Melanoma

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Over half of surgeons who reported treating melanoma with Mohs micrographic surgery (MMS) are using the technique to treat invasive melanoma, according to a national cross-sectional survey of members of the American College of Mohs Surgery.

Of 513 survey participants, 40.9% reported using MMS to treat any subtype of melanoma. Most of these surgeons reported treating both lentigo maligna (97.5%) and other melanoma in situ (MIS) subtypes (91.4%). A slight majority – 58.6% – reported treating invasive T1 melanoma, and 20.5% reported treating invasive T2 and/or higher-stage melanoma with MMS.

The analysis, published in Dermatologic Surgery, was done by Spyros M. Siscos, MD, and a team of residents and faculty in the division of dermatology at the University of Kansas Medical Center, Kansas City.

It comes on the heels of an analysis of claims data for Mohs surgery, published last year in JAMA Dermatology, which showed a more than threefold increase in the use of Mohs surgery for melanoma from 2.6% of all surgical cases in 2001 to 7.9% in 2016.

With the increased use of MMS for treatment of melanoma, “Mohs surgeons who previously treated MIS with MMS may be increasingly doing so and/or expanding their scope of treatment to include invasive melanoma,” the University of Kansas investigators wrote.

That a slight majority now report treating invasive melanoma with MMS “may be due, in part, to upstaging during the MMS procedure and the increasing evidence demonstrating improved survival of early-invasive melanoma treated with MMS compared with [wide local excision],” as well as the advent of melanocytic immunohistochemical (IHC) stains, particularly melanoma antigen recognized by T-cells 1 (MART-1), they said. However, 29% of surveyed Mohs surgeons treating melanoma with MMS do not use IHC stains “despite growing evidence supporting” their use, the authors wrote.

The advent of IHC stains, particularly MART-1, has improved the accuracy of interpreting frozen sections of melanoma, they reported, noting that MMS without IHC has been associated with a recurrence rate as high as 33%. Of the 71% who reported using IHC stains, MART-1 was the primary IHC stain for virtually all of them (97.3%).

There was also variation in the number of surgeons who reported debulking MIS. Eighty-two percent take this approach, excising the clinically visible tumor before excising the initial Mohs stage – almost all with a scalpel. More than half of these surgeons – 58.5% – submit the entire debulked MIS specimen for permanent vertical sectioning (breadloafing) to evaluate for deeper tumor invasion.

The others reported submitting the entire debulked specimen for frozen vertical sectioning, or portions of the specimen for both permanent and frozen vertical sectioning. “It is unclear why a minority of surveyed Mohs surgeons reported not debulking MIS,” wrote Dr. Siscos and his colleagues.

The average margin size of the first Mohs stage for MIS was 4.96 ± 1.74 mm, which is at the lower end of the 0.5-1.0 cm range for wide local excision (WLE) recommended by the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD), according to a clinical practice guideline. (The survey did not investigate initial margins for invasive melanoma treated with MMS.)

Jeremy R. Etzhorn, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and an author of a 2019 claims data analysis of excisional surgery practices for melanoma, said that the new survey findings – like the prior analysis – highlight the variability in approaches to using MMS for melanoma.

“Mohs for melanoma [seems] like a one-liner ... but really, there are [a lot] of different techniques that fall under that umbrella, if you parse out all the variations,” he said in an interview.

Per the 2016 claims analysis, he noted, IHC was used in less than 40% of Mohs surgery cases for melanoma, and there were wide geographic variations. “The biggest critique of Mohs surgery for melanoma over the last two decades has been that it’s hard to see the tumor,” he said. “But with the advent of IHC, that challenge was overcome.”

Surgical excision practices are evolving without the development of best practice guidelines, said Dr. Etzkorn, who is director of clinical research for the University of Pennsylvania dermatologic oncology center. Multisociety guidelines published in 2012 on appropriate use criteria for Mohs surgery do not offer specific recommendations on the use of MMS for invasive melanoma. Nor do guidelines from the AAD and the NCCN, he said.

“What this [new] study highlights and what’s being discussed amongst Moh’s surgeons” is that Mohs for melanoma “has be to be standardized” to some extent and then clinical trials conducted comparing Mohs to conventional excision. The studies that have been published in recent years comparing MMS with WLE for MIS and invasive melanoma are “not gold standard studies,” he said.

Practice guidelines then can be informed by high-quality evidence on its safety and efficacy, he said.

The 513 participants in the newly published survey represent a 31.5% response rate. Invasive T2 and/or higher stage melanoma was more likely to be treated with MMS in academic hospitals, compared with other practice settings (30.2% v. 18.1%), Dr. Siscos and his coauthors reported.

Participants who reported treating melanoma with MMS were more likely to report fellowship exposure and more likely to have received fellowship training on melanocytic IHC stains. The study “highlights the importance of fellowship exposure to MMS and IHC staining for melanoma,” the authors wrote, adding that postfellowship training opportunities in MMS and IHC staining for melanoma may help broaden its use among Mohs surgeons who received inadequate fellowship exposure.

Dr. Siscos and his colleagues reported no significant interest with commercial supporters. Dr. Etzkorn had no disclosures.

SOURCE: Siscos S et al. Dermatol Surg. 2020 Oct;46(10):1267-71.
 

Mortality in patients with COVID-19 and cancer is associated with general clinical and demographic factors, cancer-specific factors, cancer treatment variables, and laboratory parameters, according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.

Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.

The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.

Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.

Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
 

Clinical and laboratory factors: Abstract LBA72

The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.

The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.

Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).

Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).

In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).

Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
 

Treatment-related outcomes: Abstract LBA71

An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.

Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.

Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.

The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).

The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.

An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.

Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.

“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.

This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.

SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.

Mortality in patients with COVID-19 and cancer is associated with general clinical and demographic factors, cancer-specific factors, cancer treatment variables, and laboratory parameters, according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.

Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.

The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.

Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.

Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
 

Clinical and laboratory factors: Abstract LBA72

The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.

The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.

Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).

Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).

In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).

Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
 

Treatment-related outcomes: Abstract LBA71

An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.

Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.

Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.

The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).

The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.

An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.

Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.

“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.

This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.

SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.

Mortality in patients with COVID-19 and cancer is associated with general clinical and demographic factors, cancer-specific factors, cancer treatment variables, and laboratory parameters, according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.

Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.

The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.

Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.

Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
 

Clinical and laboratory factors: Abstract LBA72

The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.

The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.

Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).

Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).

In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).

Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
 

Treatment-related outcomes: Abstract LBA71

An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.

Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.

Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.

The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).

The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.

An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.

Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.

“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.

This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.

SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.

Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.

Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.

The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
 

About scoping reviews

Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.

Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:

• Establish eligibility criteria with a rationale for each criterion clearly explained
• Search multiple databases in multiple languages
• Include “gray literature,” defined as studies that are unpublished or difficult to locate
• Have several independent reviewers screen titles and abstracts
• Ask multiple independent reviewers to review full text articles
• Present results with charts or diagrams that align with the review’s objective
• Graphically depict the decision process for including/excluding sources
• Identify implications for further research.

In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.

Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
 

Findings and implications

To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.

For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.

Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).

Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).

Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
 

Care of individual patients and clinical research

National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.

In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.

Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.

The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.

Employing disease-centric and geriatric domains

Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.

Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.

As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.

An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).

Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.

Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.

These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.

Good news about cancer – with new data showing falling mortality rates and improved survival rates – is tempered somewhat by a “grim reality,” says the American Association for Cancer Research (AACR).

“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.” 

AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.

He noted that:

• Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
• Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
• Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
• Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
• In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.

“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
 

Making progress against cancer

Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.

U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.

Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.

A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.

This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.

However, both reports agree that more must be done to reduce cancer disparities even further. 

They highlight initiatives that are underway, including:

• The draft guidance issued by the FDA to promote diversification of clinical trial populations.
• The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
• The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
• The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.

Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.

Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.

Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.

“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.

Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.

The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”

Ribas further called for action from national leadership and the scientific community.

“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”

This article first appeared on Medscape.com.

Good news about cancer – with new data showing falling mortality rates and improved survival rates – is tempered somewhat by a “grim reality,” says the American Association for Cancer Research (AACR).

“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.” 

AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.

He noted that:

• Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
• Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
• Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
• Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
• In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.

“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
 

Making progress against cancer

Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.

U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.

Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.

A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.

This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.

However, both reports agree that more must be done to reduce cancer disparities even further. 

They highlight initiatives that are underway, including:

• The draft guidance issued by the FDA to promote diversification of clinical trial populations.
• The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
• The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
• The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.

Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.

Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.

Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.

“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.

Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.

The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”

Ribas further called for action from national leadership and the scientific community.

“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”

This article first appeared on Medscape.com.

Good news about cancer – with new data showing falling mortality rates and improved survival rates – is tempered somewhat by a “grim reality,” says the American Association for Cancer Research (AACR).

“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.” 

AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.

He noted that:

• Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
• Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
• Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
• Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
• In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.

“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
 

Making progress against cancer

Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.

U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.

Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.

A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.

This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.

However, both reports agree that more must be done to reduce cancer disparities even further. 

They highlight initiatives that are underway, including:

• The draft guidance issued by the FDA to promote diversification of clinical trial populations.
• The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
• The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
• The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.

Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.

Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.

Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.

“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.

Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.

The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”

Ribas further called for action from national leadership and the scientific community.

“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”

This article first appeared on Medscape.com.

Patients with advanced melanoma who have progressed on anti–programmed death 1/PD-ligand 1 (PD-L1) immunotherapy could substantially extend their overall survival (OS) with a combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and pembrolizumab (Keytruda), suggests an open-label, single arm study.

The research was presented Sept. 19 at the European Society for Medical Oncology Virtual Congress 2020.

In LEAP-004 trial, over 100 patients with stage 3 or 4 melanoma who had progressed after immunotherapy were given lenvatinib plus pembrolizumab, which yielded a median progression-free survival (PFS) of more than 4 months and a median OS of more than a year. Median follow-up was 12 months.

Presenting the findings, Ana Maria Arance Fernandez, MD, PhD, Hospital Clínic de Barcelona, Spain, said lenvatinib plus pembrolizumab has “promising” antitumor activity in patients with advanced melanoma with confirmed progression on a PD-1 inhibitor given alone or in combination. “These results are encouraging given the stringent definition of progression on prior anti-PD-1 therapy and the enrollment of poor-risk patients.”

Dr. Arance Fernandez added that “these data support lenvatinib plus pembrolizumab as a potential treatment regimen for this population of high unmet medical need.”

Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was not involved in the study, discussed the findings.

He highlighted that the patients were not randomly assigned in LEAP-004, with all of them receiving the same therapy.

Nevertheless, the response rate was “quite impressive for this patient population.”

He also drew comparison with previous data with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) in a similar population, noting that the overall survival was less than half that seen in the current trial, “which makes these results even more important.”

“It tells us that this combination might be an option with disease progression on anti-PD-1,” Dr. Chmielowski noted.

Dr. Arance Fernandez pointed out that patients with advanced melanoma who progress on standard-of-care treatment with anti-PD-1 therapy or a cytotoxic T-lymphocyte–associated protein 4 (CTLA4) inhibitor plus anti-PD-1 “have very limited therapeutic options available and there is no approved regimen in this indication.”
 

Response rate, PFS, and OS

Previous studies have indicated that adding an anti-PD-1 drug to lenvatinib achieves superior antitumor activity than either treatment alone, with promising results in phase 1/2b data in pretreated metastatic melanoma.

LEAP-004 therefore enrolled patients with unresectable stage 3 or 4 melanoma, who had disease progression within 12 weeks of their last dose of anti-PD-(L)1 therapy either alone or with a CTLA4 inhibitor. There was no limit on the number of prior treatments.

The patients received pembrolizumab 200 mg IV for up to 35 cycles plus lenvatinib 20 mg daily until progression, unacceptable toxicity, or patient or physician decision.

They were imaged at baseline and every 9 weeks through to week 54, then every 12 weeks until week 102, and then every 24 weeks.

From February to September 2019, 103 patients were enrolled, all of whom received at least one dose of lenvatinib plus pembrolizumab. The median age of the patients was 63 years, and 53.4% were male.

Dr. Arance Fernandez pointed out that this was a high-risk population, with 20.4% having a lactate dehydrogenase level twice the upper limit of normal and 14.6% having brain metastasis, while the median sum of target lesions was 100 mm.

A BRAFv600 mutation was identified in 36.9% of patients, and 64.1% were PD-L1 positive.

Nearly one third (28.2%) had received a prior anti-CTLA4 plus anti-PD-(L)1 combination, and 19.5% had undergone four or more prior lines of therapy.

The overall response rate to lenvatinib plus pembrolizumab was 21.4%, with 1.9% having a complete response and 19.4% a partial response. This was seen across subgroups, including by age and disease stage.

Dr. Arance Fernandez said the overall response rate was even higher in patients who had previously been treated with an anti-CTLA4 plus anti-PD-(L)1 combination, at 31%.

However, Dr. Chmielowski warned that “we must interpret this result with caution since only 29 patients were in this subpopulation.”

The median duration of response (per blinded independent committee review) across the study population was 6.3 months, with 72.6% still responding at 6 months.

The median PFS was 4.2 months with the combination therapy, with 41.7% of patients progression free at 6 months, and 26.2% at 9 months.

Median overall survival was 13.9 months, with 77.3% of patients still alive at 6 months and 65.4% alive at 9 months.

Although 96.1% of patients experienced at least one treatment-related adverse event of any grade, only 44.7% had grade 3 or higher events, and only in 7.8% of cases did that lead to treatment discontinuation.

The most common adverse events were hypertension (56.3%), diarrhea (35.9%), nausea (34%), and hypothyroidism (33%), although, in the vast majority of cases, these events were grade 1 or 2.
 

LEAP presents challenges

Dr. Chmielowski would like to see treatment in this setting individualized somehow.

“It will be also important to come up with personalized immunotherapy so that, based on the mechanism of resistance in patient populations, we would be able to choose the subsequent treatments,” he commented.

Dr. Arance Fernandez explained that lenvatinib inhibits multiple tyrosine kinases involved in angiogenesis, cell proliferation, and immune modulation, and has demonstrated immunomodulatory activity in the tumor microenvironment.

However, Dr. Arance Fernandez noted that, as resistance to immunotherapy is “multifactorial,” it may be that a combination treatment will be more effective in these patients.

The study was funded by Merck. Dr. Arance Fernandez has financial ties to Merck and multiple other drug companies. Dr. Chmielowski has financial ties to Merck Serono and multiple other companies.  

This article first appeared on Medscape.com.

Patients with advanced melanoma who have progressed on anti–programmed death 1/PD-ligand 1 (PD-L1) immunotherapy could substantially extend their overall survival (OS) with a combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and pembrolizumab (Keytruda), suggests an open-label, single arm study.

The research was presented Sept. 19 at the European Society for Medical Oncology Virtual Congress 2020.

In LEAP-004 trial, over 100 patients with stage 3 or 4 melanoma who had progressed after immunotherapy were given lenvatinib plus pembrolizumab, which yielded a median progression-free survival (PFS) of more than 4 months and a median OS of more than a year. Median follow-up was 12 months.

Presenting the findings, Ana Maria Arance Fernandez, MD, PhD, Hospital Clínic de Barcelona, Spain, said lenvatinib plus pembrolizumab has “promising” antitumor activity in patients with advanced melanoma with confirmed progression on a PD-1 inhibitor given alone or in combination. “These results are encouraging given the stringent definition of progression on prior anti-PD-1 therapy and the enrollment of poor-risk patients.”

Dr. Arance Fernandez added that “these data support lenvatinib plus pembrolizumab as a potential treatment regimen for this population of high unmet medical need.”

Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was not involved in the study, discussed the findings.

He highlighted that the patients were not randomly assigned in LEAP-004, with all of them receiving the same therapy.

Nevertheless, the response rate was “quite impressive for this patient population.”

He also drew comparison with previous data with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) in a similar population, noting that the overall survival was less than half that seen in the current trial, “which makes these results even more important.”

“It tells us that this combination might be an option with disease progression on anti-PD-1,” Dr. Chmielowski noted.

Dr. Arance Fernandez pointed out that patients with advanced melanoma who progress on standard-of-care treatment with anti-PD-1 therapy or a cytotoxic T-lymphocyte–associated protein 4 (CTLA4) inhibitor plus anti-PD-1 “have very limited therapeutic options available and there is no approved regimen in this indication.”
 

Response rate, PFS, and OS

Previous studies have indicated that adding an anti-PD-1 drug to lenvatinib achieves superior antitumor activity than either treatment alone, with promising results in phase 1/2b data in pretreated metastatic melanoma.

LEAP-004 therefore enrolled patients with unresectable stage 3 or 4 melanoma, who had disease progression within 12 weeks of their last dose of anti-PD-(L)1 therapy either alone or with a CTLA4 inhibitor. There was no limit on the number of prior treatments.

The patients received pembrolizumab 200 mg IV for up to 35 cycles plus lenvatinib 20 mg daily until progression, unacceptable toxicity, or patient or physician decision.

They were imaged at baseline and every 9 weeks through to week 54, then every 12 weeks until week 102, and then every 24 weeks.

From February to September 2019, 103 patients were enrolled, all of whom received at least one dose of lenvatinib plus pembrolizumab. The median age of the patients was 63 years, and 53.4% were male.

Dr. Arance Fernandez pointed out that this was a high-risk population, with 20.4% having a lactate dehydrogenase level twice the upper limit of normal and 14.6% having brain metastasis, while the median sum of target lesions was 100 mm.

A BRAFv600 mutation was identified in 36.9% of patients, and 64.1% were PD-L1 positive.

Nearly one third (28.2%) had received a prior anti-CTLA4 plus anti-PD-(L)1 combination, and 19.5% had undergone four or more prior lines of therapy.

The overall response rate to lenvatinib plus pembrolizumab was 21.4%, with 1.9% having a complete response and 19.4% a partial response. This was seen across subgroups, including by age and disease stage.

Dr. Arance Fernandez said the overall response rate was even higher in patients who had previously been treated with an anti-CTLA4 plus anti-PD-(L)1 combination, at 31%.

However, Dr. Chmielowski warned that “we must interpret this result with caution since only 29 patients were in this subpopulation.”

The median duration of response (per blinded independent committee review) across the study population was 6.3 months, with 72.6% still responding at 6 months.

The median PFS was 4.2 months with the combination therapy, with 41.7% of patients progression free at 6 months, and 26.2% at 9 months.

Median overall survival was 13.9 months, with 77.3% of patients still alive at 6 months and 65.4% alive at 9 months.

Although 96.1% of patients experienced at least one treatment-related adverse event of any grade, only 44.7% had grade 3 or higher events, and only in 7.8% of cases did that lead to treatment discontinuation.

The most common adverse events were hypertension (56.3%), diarrhea (35.9%), nausea (34%), and hypothyroidism (33%), although, in the vast majority of cases, these events were grade 1 or 2.
 

LEAP presents challenges

Dr. Chmielowski would like to see treatment in this setting individualized somehow.

“It will be also important to come up with personalized immunotherapy so that, based on the mechanism of resistance in patient populations, we would be able to choose the subsequent treatments,” he commented.

Dr. Arance Fernandez explained that lenvatinib inhibits multiple tyrosine kinases involved in angiogenesis, cell proliferation, and immune modulation, and has demonstrated immunomodulatory activity in the tumor microenvironment.

However, Dr. Arance Fernandez noted that, as resistance to immunotherapy is “multifactorial,” it may be that a combination treatment will be more effective in these patients.

The study was funded by Merck. Dr. Arance Fernandez has financial ties to Merck and multiple other drug companies. Dr. Chmielowski has financial ties to Merck Serono and multiple other companies.  

This article first appeared on Medscape.com.

Patients with advanced melanoma who have progressed on anti–programmed death 1/PD-ligand 1 (PD-L1) immunotherapy could substantially extend their overall survival (OS) with a combination of the tyrosine kinase inhibitor lenvatinib (Lenvima) and pembrolizumab (Keytruda), suggests an open-label, single arm study.

The research was presented Sept. 19 at the European Society for Medical Oncology Virtual Congress 2020.

In LEAP-004 trial, over 100 patients with stage 3 or 4 melanoma who had progressed after immunotherapy were given lenvatinib plus pembrolizumab, which yielded a median progression-free survival (PFS) of more than 4 months and a median OS of more than a year. Median follow-up was 12 months.

Presenting the findings, Ana Maria Arance Fernandez, MD, PhD, Hospital Clínic de Barcelona, Spain, said lenvatinib plus pembrolizumab has “promising” antitumor activity in patients with advanced melanoma with confirmed progression on a PD-1 inhibitor given alone or in combination. “These results are encouraging given the stringent definition of progression on prior anti-PD-1 therapy and the enrollment of poor-risk patients.”

Dr. Arance Fernandez added that “these data support lenvatinib plus pembrolizumab as a potential treatment regimen for this population of high unmet medical need.”

Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who was not involved in the study, discussed the findings.

He highlighted that the patients were not randomly assigned in LEAP-004, with all of them receiving the same therapy.

Nevertheless, the response rate was “quite impressive for this patient population.”

He also drew comparison with previous data with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) in a similar population, noting that the overall survival was less than half that seen in the current trial, “which makes these results even more important.”

“It tells us that this combination might be an option with disease progression on anti-PD-1,” Dr. Chmielowski noted.

Dr. Arance Fernandez pointed out that patients with advanced melanoma who progress on standard-of-care treatment with anti-PD-1 therapy or a cytotoxic T-lymphocyte–associated protein 4 (CTLA4) inhibitor plus anti-PD-1 “have very limited therapeutic options available and there is no approved regimen in this indication.”
 

Response rate, PFS, and OS

Previous studies have indicated that adding an anti-PD-1 drug to lenvatinib achieves superior antitumor activity than either treatment alone, with promising results in phase 1/2b data in pretreated metastatic melanoma.

LEAP-004 therefore enrolled patients with unresectable stage 3 or 4 melanoma, who had disease progression within 12 weeks of their last dose of anti-PD-(L)1 therapy either alone or with a CTLA4 inhibitor. There was no limit on the number of prior treatments.

The patients received pembrolizumab 200 mg IV for up to 35 cycles plus lenvatinib 20 mg daily until progression, unacceptable toxicity, or patient or physician decision.

They were imaged at baseline and every 9 weeks through to week 54, then every 12 weeks until week 102, and then every 24 weeks.

From February to September 2019, 103 patients were enrolled, all of whom received at least one dose of lenvatinib plus pembrolizumab. The median age of the patients was 63 years, and 53.4% were male.

Dr. Arance Fernandez pointed out that this was a high-risk population, with 20.4% having a lactate dehydrogenase level twice the upper limit of normal and 14.6% having brain metastasis, while the median sum of target lesions was 100 mm.

A BRAFv600 mutation was identified in 36.9% of patients, and 64.1% were PD-L1 positive.

Nearly one third (28.2%) had received a prior anti-CTLA4 plus anti-PD-(L)1 combination, and 19.5% had undergone four or more prior lines of therapy.

The overall response rate to lenvatinib plus pembrolizumab was 21.4%, with 1.9% having a complete response and 19.4% a partial response. This was seen across subgroups, including by age and disease stage.

Dr. Arance Fernandez said the overall response rate was even higher in patients who had previously been treated with an anti-CTLA4 plus anti-PD-(L)1 combination, at 31%.

However, Dr. Chmielowski warned that “we must interpret this result with caution since only 29 patients were in this subpopulation.”

The median duration of response (per blinded independent committee review) across the study population was 6.3 months, with 72.6% still responding at 6 months.

The median PFS was 4.2 months with the combination therapy, with 41.7% of patients progression free at 6 months, and 26.2% at 9 months.

Median overall survival was 13.9 months, with 77.3% of patients still alive at 6 months and 65.4% alive at 9 months.

Although 96.1% of patients experienced at least one treatment-related adverse event of any grade, only 44.7% had grade 3 or higher events, and only in 7.8% of cases did that lead to treatment discontinuation.

The most common adverse events were hypertension (56.3%), diarrhea (35.9%), nausea (34%), and hypothyroidism (33%), although, in the vast majority of cases, these events were grade 1 or 2.
 

LEAP presents challenges

Dr. Chmielowski would like to see treatment in this setting individualized somehow.

“It will be also important to come up with personalized immunotherapy so that, based on the mechanism of resistance in patient populations, we would be able to choose the subsequent treatments,” he commented.

Dr. Arance Fernandez explained that lenvatinib inhibits multiple tyrosine kinases involved in angiogenesis, cell proliferation, and immune modulation, and has demonstrated immunomodulatory activity in the tumor microenvironment.

However, Dr. Arance Fernandez noted that, as resistance to immunotherapy is “multifactorial,” it may be that a combination treatment will be more effective in these patients.

The study was funded by Merck. Dr. Arance Fernandez has financial ties to Merck and multiple other drug companies. Dr. Chmielowski has financial ties to Merck Serono and multiple other companies.  

This article first appeared on Medscape.com.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.

The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.

The findings were published online on September 2 in the BMJ.

The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.

The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.

Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.

A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).

“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.

“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.

A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.

Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.

“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.

However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”

But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”

Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.

That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
 

With changes in the 1980s, even safer now?

The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.

Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.

The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.

Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.

However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).

“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
 

Study details

The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.

Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).

As noted above, there were some exceptions.

Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.

Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).

In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).

In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”

She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).

Geographic location is a particularly important variable, suggested the study authors.

They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”

The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.

New data show that the benefit is maintained over the longer term.

At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) conferred a durable long-term, relapse-free survival benefit for patients with resected stage III melanoma with BRAF V600E or V600K mutations, the investigators concluded.

These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.

“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”

Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”

“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”

In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”

As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.

“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.

“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”

“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.


 

Study details

The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.

Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.

Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.

Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.

At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).

The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).

The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.

Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
 

A viable option

Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”

He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.

The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.

A version of this article originally appeared on Medscape.com.

Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.

New data show that the benefit is maintained over the longer term.

At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) conferred a durable long-term, relapse-free survival benefit for patients with resected stage III melanoma with BRAF V600E or V600K mutations, the investigators concluded.

These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.

“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”

Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”

“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”

In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”

As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.

“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.

“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”

“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.


 

Study details

The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.

Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.

Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.

Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.

At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).

The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).

The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.

Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
 

A viable option

Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”

He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.

The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.

A version of this article originally appeared on Medscape.com.

Adjuvant therapy for patients with high-risk resected melanomas is now a standard of care, but the durability of the benefit gained from this treatment is still unclear.

New data show that the benefit is maintained over the longer term.

At 5 years, just over half of patients (52%) with advanced melanoma who had received a year of adjuvant therapy with two targeted agents were still alive and remained relapse free, compared with 36% of patients who received placebo.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) conferred a durable long-term, relapse-free survival benefit for patients with resected stage III melanoma with BRAF V600E or V600K mutations, the investigators concluded.

These data come from the COMBI-AD phase 3 trial and were published online in the New England Journal of Medicine.

“The treatment duration of this adjuvant therapy was 12 months; however, we do not know whether this is the optimal treatment duration,” said lead author Reinhard Dummer, MD, vice chairman, department of dermatology, University of Zürich Hospital. “Early biomarker results suggest that, in a subgroup, longer treatment durations might be necessary. In other patients, a shorter treatment could be sufficient.”

Richard Carvajal, MD, director of the Melanoma Service at New York–Presbyterian Hospital and Columbia University Medical Center, also in New York, said the new data “address prior concerns that any benefit achieved with targeted therapy in the adjuvant setting may be limited in duration.”

“Indeed, with active therapy, over 50% of patients are alive without relapse and 65% of patients are alive without the development of distant metastasis,” he said. “Although overall survival data remain immature, numerical improvement in survival is also reported.”

In an interview, Dr. Carvajal said that the plateaus observed with relapse and distant metastasis-free survival suggest that true disease cures are being achieved with treatment. “Based upon these results, the discussion of adjuvant therapeutic options should include a 12-month course of adjuvant dabrafenib and trametinib, as well as the option of adjuvant anti-PD-1 [programmed death–1] therapy.”

As for how the MEK-BRAF inhibitor combination compares with immunotherapy in this setting, he pointed out that, since there has been no head-to-head comparison of adjuvant targeted therapy and adjuvant nivolumab (Opdivo) or pembrolizumab (Keytruda), it is not possible to conclusively state that one regimen is more effective than another.

“For patients with resected BRAF-mutant melanoma at high risk of disease recurrence, we now have data demonstrating the clinical benefit for a course of adjuvant dabrafenib and trametinib, adjuvant nivolumab and adjuvant pembrolizumab,” said Dr. Carvajal.

“Although the efficacy of adjuvant ipilimumab [Yervoy] as well as adjuvant interferon have also been previously demonstrated, these agents are now appropriate for consideration in extremely rare clinical circumstances given the clinical efficacy and improved toxicity profile of single agent anti-PD-1 therapy.”

“The selection of the most appropriate adjuvant therapy should take into account the preferences of individual patients in terms of toxicity profile and drug administration considerations,” he added.


 

Study details

The COMBI-AD was a randomized, double-blind, placebo-controlled, phase 3 study conducted in 870 patients with high-risk, stage III, BRAF-V600E/K–mutant melanoma who were treatment naive. Participating patients had undergone surgical resection and had been disease free for ≤12 weeks.

Interim results from this study, reported in 2017, showed 1 year of oral adjuvant therapy with dabrafenib and trametinib provided a 53% lower risk for 3-year recurrence, compared with placebo.

Now, the investigators reported on the 5-year results for relapse-free survival and survival without distant metastasis. They noted that they were unable to analyze overall survival since the required number of events had not been reached.

Patients had been randomly assigned to receive 12 months of oral dabrafenib (at a dose of 150 mg twice daily) plus trametinib (2 mg once daily) or two matched placebos. Patients were followed for 60 months (5 years) for dabrafenib plus trametinib and 58 months for placebo.

At 5 years, the median relapse-free survival was not reached for patients who received the combination therapy group versus 16.6 months in the placebo group (hazard ratio for relapse or death, 0.51).

The percentage of patients who were alive without distant metastasis at 5 years was 65% in the dabrafenib plus trametinib group and 54% in the placebo arm (HR for distant metastasis or death, 0.55).

The hazard ratio for relapse-free survival favored dabrafenib plus trametinib across all patient subgroups that were evaluated in the study, and survival without distant metastasis showed a similar benefit for the combination regardless of disease stage.

Subsequent therapy was needed in 40% of patients who received dabrafenib plus trametinib and by 54% of those in the placebo group, with the most common treatments being immunotherapy in the combination-therapy group [26%] and small molecule–targeted therapy in the placebo group (35%).
 

A viable option

Dr. Dummer noted that, when this clinical trial was designed, all patients had to undergo aggressive surgery that involved lymph node dissection. “Nowadays, based on the lack of improvement on progression-free survival and overall survival, the surgical procedures are less aggressive and today we do not recommend aggressive lymph node dissection in patients that qualify for adjuvant therapy. In patients that do not have the BRAF mutation, there is the possibility of giving immunotherapy.”

He added that there is an urgent need for biomarkers that can identify early progression during adjuvant therapy. “Potentially, these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy,” Dr. Dummer said.

The study was funded by GlaxoSmithKline and Novartis. Dr. Dummer has declared multiple relationships with industry.

A version of this article originally appeared on Medscape.com.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.

Malignant melanomas in children and adolescents are thankfully rare, but they can be challenging to diagnose, and fatal disease can manifest itself in any of several different ways, results of a retrospective multicenter study showed.

“The most striking thing that we learned from this study is that pediatric melanoma can present in so many different ways, and it’s distinct from the adult population in that we see more presentations associated with congenital nevi, or spitz melanoma, which is a special class of pigmented lesions that looks a little different under the microscope,” Elena B. Hawryluk, MD, PhD, of the department of dermatology at Massachusetts General Hospital (MGH) and Harvard University, Boston, said in an interview. Dr. Hawryluk is lead author of the study, which was published online ahead of print in the Journal of the American Academy of Dermatology.

Dr. Hawryluk and colleagues at MGH and 11 other centers conducted a retrospective review of all cases of fatal pediatric melanoma among patients younger than 20 years diagnosed from late 1994 through early 2017.

They identified a total of 38 fatal cases over more than 2 decades. The cases were distinguished primarily by their heterogeneous clinical presentation and by the diversity of the patients, their precursor lesions, and the tumor histopathology, she said in an interview.

“We were surprised to find that patients with each of these presentations could end up with a fatal course, it wasn’t just all the adolescents, or all the patients with giant congenital nevi; it really presented quite diversely.”
 

Rare malignancy

Melanoma is far less common in the pediatric population than in adults, with an annual incidence of 18 per 1 million among adolescents aged 15-18 years, and 1 per 1 million in children under 10 years, the authors noted.

“Melanoma in children and adolescents often has distinct clinical presentations such as association with a congenital melanocytic nevus (CMN), spitzoid melanoma, or amelanotic melanoma, which are more rarely observed in adult melanoma patients. Unique pediatric-specific clinical detection criteria have been proposed to highlight these differences, such as a tendency to present amelanotically,” they wrote.

Factors associated with worse prognosis, such as higher Breslow thickness and mitotic index, are more frequently present at the time of diagnosis in children compared with adults, particularly those diagnosed before age 11 years.

“It is unclear if this difference is secondary to diagnostic delays due to low clinical suspicion, atypical clinical presentations, or more rapid tumor growth rate, as many childhood melanomas are of nodular or spitzoid subtypes,” Dr. Hawryluk and her coauthors wrote.
 

Study details

The investigators sought to characterize the clinical and histopathologic features of fatal pediatric melanomas.

They found that 21 of the 38 patients (57%) were of White heritage, 7 (19%) were of Hispanic or Latino background, 1 (3%) was of Asian lineage, and 1 each were of Black African American or Black Hispanic background. The remaining children were classified as “other” or did not have their ethnic backgrounds recorded.

The “striking prevalence” of Hispanic patients observed in the study is consistent with surveillance reports of an increasing incidence of melanoma among children of Hispanic background, they noted.

The mean age at diagnosis was 12.7 years, and the mean age at death was 15.6 years.

Of the 16 cases with known identifiable disease subtypes, 8 (50%) were nodular, 5 (31%) were superficial spreading, and 3 (19%) were spitzoid melanomas. Of the 38 fatal melanomas, 10 were thought to have originated from congenital melanocytic nevi.
 

Outlook improving

Recent therapeutic breakthroughs such as targeted agents and immunotherapy with checkpoint inhibitors augur well for children diagnosed with melanoma, Dr. Hawryluk said.

“Fortunately, it’s not superaggressive in children at high frequency, so we generally use adult algorithms to inform treatment decisions,” she said. “It’s just important to note that melanomas that arise in congenital nevi tend to have different driver mutations than those that arise in older patients who may have lots of sun exposure.”

“Nowadays, we’re lucky to have a lot of extra tests and workups so that, if a patient does have metastatic or advance disease, they can have a better genetic profile that would guide our choice of medications,” she added.

The study was supported by a Pediatric Dermatology Research Alliance Study Support grant and Society for Pediatric Dermatology, Pediatric Dermatology Research Alliance Pilot award. Dr. Hawryluk is supported by the Dermatology Foundation and the Harvard Medical School Eleanor and Miles Shore Fellowship award. The authors reported no conflicts of interest.

SOURCE: Hawryluk EB et al. J Am Acad Dermatol. 2020 Jul 1. doi: 10.1016/j.jaad.2020.06.1010.