Lung Cancer

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

In an international survey, most oncologists said they would recommend cytotoxic chemotherapy, immune checkpoint inhibitors, and steroids less often during the COVID-19 pandemic.

While neoadjuvant treatment recommendations were not strongly affected by the pandemic, about half of oncologists reported increased hesitancy over recommending frontline chemotherapy for metastatic disease, and a vast majority said they would recommend second- or third-line chemotherapy less often in the metastatic setting.

Most oncologists said they did not perform routine COVID-19 testing via reverse transcriptase–polymerase chain reaction (RT-PCR) before treating cancer patients. In fact, only 3% said they performed COVID-19 RT-PCR testing routinely.

Yüksel Ürün, MD, of Ankara (Turkey) University, and colleagues reported these findings in JCO Global Oncology.

The goal of the survey was to “understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision-making was influenced by the pandemic,” the authors wrote.

The online survey was conducted among 343 oncologists from 28 countries. Responses were collected anonymously, a majority (71%) from university or academic centers, with 95% received between April 1 and April 29, 2020.

Use of telemedicine was common (80%) among respondents, as was use of surgical masks (90%) and personal protective equipment in general.

Only 33% of respondents described using N95 masks. However, the proportion of oncologists who had access to N95 masks while caring for patients known to have COVID-19, especially while doing invasive procedures such as intubation, bronchoscopy, and any airway-related manipulations, was not captured by the survey.
 

COVID testing and cancer treatment

Most respondents (58%) said they did not perform routine COVID-19 RT-PCR testing prior to administering systemic cancer treatment, with 39% stating they performed RT-PCR tests in selected patients, and 3% saying they performed such testing in all patients.

The survey indicated that hormonal treatments, tyrosine kinase inhibitors, and bone-modifying agents were considered relatively safe, but cytotoxic chemotherapy and immune therapies were not.

Nearly all oncologists said the pandemic would cause them to make no change to their recommendations regarding hormone therapy, and nearly 80% said they would make no changes regarding tyrosine kinase inhibitors or bone-modifying agents.

However, more than 90% of respondents said they would recommend cytotoxic chemotherapy less often, about 70% said they would recommend corticosteroids less often, and around 50% said they would recommend anti–programmed death-1/PD-ligand 1 or anti–cytotoxic T-lymphocyte–associated protein 4 antibodies less often.

The pandemic made most respondents more reluctant to recommend second- or third-line chemotherapy in the metastatic setting. About 80% and 70% of respondents, respectively, would recommend second- or third-line chemotherapy less often.

However, first-line chemotherapy for metastatic disease, as well as adjuvant and neoadjuvant therapy, were less affected. About 30% of respondents said they would recommend neoadjuvant therapy less often, and 50%-55% would recommend adjuvant therapy or frontline chemotherapy for metastatic disease less often.

Most respondents (78%) said they would use granulocyte colony–stimulating factor (G-CSF) more frequently during the pandemic.

The factors most likely to affect oncologists’ treatment decisions were patient age (81%) and concomitant disease (92%). Additionally, 80% of respondents’ treatment decisions were influenced by Eastern Cooperative Oncology Group performance status of 2 or higher, or the presence of chronic obstructive pulmonary disease.

Interpretation and implications

“These results highlight that, even in the early phases of COVID-19 – during which there was considerable uncertainty – basic core principles were guideposts for oncologists,” observed Aly-Khan Lalani, MD, of Juravinski Cancer Centre and McMaster University, Hamilton, Ont., who was not involved in this study.

“For example, [oncologists were] prioritizing strategies for treatments with the largest expected impact and carefully tailoring treatment according to patient comorbidities and performance status,” Dr. Lalani said.

Another oncologist who was not involved in the study expressed concern over reductions in adjuvant therapy supported by half of oncologists surveyed.

“Although benefits may be marginal in some cases, these are curative settings and especially warrant careful individual-level risk/benefit discussions,” said Kartik Sehgal, MD, of Dana-Farber Cancer Institute/Brigham and Women’s Hospital in Boston.

His concern extended as well to the small proportion (3%) of oncologists testing for COVID-19 in all patients. “Systematic testing is the need of the hour,” Dr. Sehgal said.

In their discussion of the findings, Dr. Ürün and colleagues noted a lack of consensus on monoclonal antibody and immunotherapy safety among surveyed oncologists. The steroids needed to manage severe immune-mediated toxicity with immune checkpoint inhibitors has led to some prescribing reluctance during the pandemic.

Immunosuppressive properties of immune checkpoint inhibitors also raise concern that they can increase COVID-19 severity. Studies are few, and findings to date are inconsistent with respect to the effect of immune checkpoint inhibitors on COVID-19 clinical course. However, a recently presented study suggested that immune checkpoint inhibitors do not increase the risk of death among cancer patients with COVID-19 (AACR: COVID-19 and Cancer, Abstract S02-01).

Dr. Ürün and colleagues noted that greater COVID-19 severity has been shown in patients with performance status greater than 1, hematologic malignancies, lung cancer, stage IV metastatic disease, chemotherapy within the prior 3 months, cancer treatment in the last 14 days, and the presence of chronic obstructive pulmonary disease. Nonmetastatic cancer has not been shown to affect COVID-19 severity, however.

Dr. Ürün and colleagues also underscored the need for research evidence to balance potential reductions in neutropenic complications with G-CSF (and therefore, reduced hospitalizations) with a theoretical risk of G-CSF–mediated pulmonary injury through its stimulation of an excessive immune response.

Finally, the authors urged oncologists to evaluate each proposed therapy’s risk/benefit ratio on an individual patient basis, and the team tasked the oncology community with gathering comprehensive, rigorous data.

There was no funding source declared for this study. Dr. Ürün and colleagues disclosed various relationships with many pharmaceutical companies, which included receiving research funding. Dr. Sehgal and Dr. Lalani reported no relevant conflicts.
 

SOURCE: Ürün Y et al. JCO Glob Oncol. 2020 Aug;6:1248-57.

Mortality from non–small cell lung cancer (NSCLC) has fallen sharply in the United States over the past few years, and survival following its diagnosis has dramatically improved, the first analysis of its kind indicates.

“This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, NSCLC, are declining faster than its incidence, an advance that correlates with the [FDA] approval of several targeted therapies for this cancer in recent years,” coauthor Douglas Lowy, MD, deputy director, National Cancer Institute, Bethesda, Md., said in a statement.

“Major improvements have been made in NSCLC treatment with the advent of targeted therapies and immunotherapies,” lead author Nadia Howlander, PhD, National Cancer Institute, and colleagues observed.

“The survival benefit for patients with NSCLC treated with targeted therapy has been shown in clinical trials, but our study highlights their possible effect at the population level,” they added.

In contrast, mortality from SCLC has dropped only in tandem with a decline in the incidence of SCLC, and survival has remained largely unchanged, the same analysis showed.

NSCLC is by far the most common type of lung cancer, accounting for more than 75% of all lung cancer cases in the United States. SCLC accounts for about 13%.

The study was published online Aug. 12 in the New England Journal of Medicine.

“Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information,” the authors commented.

“To address this data limitation, the U.S. Surveillance, Epidemiology and End Results (SEER) program has linked mortality records to incidence cancer cases,” the authors explained. This allowed them to calculate incidence-based mortality among men and women in the United States.

The incidence-based mortality method that the researchers used was applied to the SEER data to describe population-level mortality trends in the United States that were attributable to each subtype of lung cancer as well as gender from 2001 to 2016.

Among men, the incidence of NSCLC decreased gradually by 1.9% a year from 2001 to 2008, then more dramatically by 3.1% a year from 2008 to 2016.

Corresponding incidence-based mortality rates among men dropped by 3.2% a year from 2006 to 2013, then again more dramatically by 6.3% a year from 2013 to 2016.

“The 2-year relative survival among patients with lung cancer improved substantially from 26% among men with NSCLC diagnosed in 2001 to 35% among those with NSCLC diagnosed in 2014,” the researchers added.

Among women, the incidence of NSCLC remained unchanged between 2001 and 2006, after which it began to drop by 1.5% a year from 2006 to 2016.

“In contrast, incidence-based mortality decreased slowly [among women] by 2.3% annually ... from 2006 through 2014 and then at a faster rate of 5.9% annually ... from 2014 through 2016,” the authors noted.

The 2-year relative survival rate for patients with NSCLC was higher among women than among men, improving from 35% in 2001 to 44% in 2014.

Improvements in survival were also observed for all races and ethnicities, despite concerns that new cancer treatments might increase treatment disparities between races, because they are all so expensive, the authors commented.

Mortality from SCLC declined by 4.3% a year among men, but that decline was entirely due to a similar decrease in the incidence of SCLC. Survival at 2 years for patients with this subtype of lung cancer remained largely unchanged over the same interval.

Genetic testing

The accelerating decline in NSCLC mortality starting in 2013 corresponds to the period in which clinicians began to routinely test for molecular alterations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), the authors pointed out.

In 2012, the National Comprehensive Cancer Network recommended that all patients with nonsquamous NSCLC undergo genetic testing for EGFR mutations and ALK rearrangements.

At about the same time, the FDA approved a number of targeted therapies for tumors that are sensitive to targeted tyrosine kinase inhibition.

More recently, immunotherapies that act as programmed cell death inhibitors have substantially improved NSCLC outcomes, the authors noted.

The first of these was approved for NSCLC in 2015 (pembrolizumab). It was followed by a number of similar agents. It is unlikely that their approval contributed to the observed decline in NSCLC mortality, which started to accelerate in 2013 in the United States, the authors commented.

Nevertheless, the effect that the immune checkpoint inhibitors has had on the survival of patients with NSCLC can be expected to continue and to extend improvement in survival beyond the current study endpoint in 2016, they suggest.

Another contributing factor is the decline in smoking that has occurred in the United States since the 1960s. This has led to the decrease in the incidence of lung cancer. The faster decrease in the incidence of SCLC, compared with NSCLC can be explained by the higher relative risk of smoking with regard to SCLC compared to NSCLC, they commented.

Similarly, the faster decrease in lung cancer incidence in men compared to women can be explained by the relative difference in the prevalence of smoking between men and women, they added.

The authors disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Mortality from non–small cell lung cancer (NSCLC) has fallen sharply in the United States over the past few years, and survival following its diagnosis has dramatically improved, the first analysis of its kind indicates.

“This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, NSCLC, are declining faster than its incidence, an advance that correlates with the [FDA] approval of several targeted therapies for this cancer in recent years,” coauthor Douglas Lowy, MD, deputy director, National Cancer Institute, Bethesda, Md., said in a statement.

“Major improvements have been made in NSCLC treatment with the advent of targeted therapies and immunotherapies,” lead author Nadia Howlander, PhD, National Cancer Institute, and colleagues observed.

“The survival benefit for patients with NSCLC treated with targeted therapy has been shown in clinical trials, but our study highlights their possible effect at the population level,” they added.

In contrast, mortality from SCLC has dropped only in tandem with a decline in the incidence of SCLC, and survival has remained largely unchanged, the same analysis showed.

NSCLC is by far the most common type of lung cancer, accounting for more than 75% of all lung cancer cases in the United States. SCLC accounts for about 13%.

The study was published online Aug. 12 in the New England Journal of Medicine.

“Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information,” the authors commented.

“To address this data limitation, the U.S. Surveillance, Epidemiology and End Results (SEER) program has linked mortality records to incidence cancer cases,” the authors explained. This allowed them to calculate incidence-based mortality among men and women in the United States.

The incidence-based mortality method that the researchers used was applied to the SEER data to describe population-level mortality trends in the United States that were attributable to each subtype of lung cancer as well as gender from 2001 to 2016.

Among men, the incidence of NSCLC decreased gradually by 1.9% a year from 2001 to 2008, then more dramatically by 3.1% a year from 2008 to 2016.

Corresponding incidence-based mortality rates among men dropped by 3.2% a year from 2006 to 2013, then again more dramatically by 6.3% a year from 2013 to 2016.

“The 2-year relative survival among patients with lung cancer improved substantially from 26% among men with NSCLC diagnosed in 2001 to 35% among those with NSCLC diagnosed in 2014,” the researchers added.

Among women, the incidence of NSCLC remained unchanged between 2001 and 2006, after which it began to drop by 1.5% a year from 2006 to 2016.

“In contrast, incidence-based mortality decreased slowly [among women] by 2.3% annually ... from 2006 through 2014 and then at a faster rate of 5.9% annually ... from 2014 through 2016,” the authors noted.

The 2-year relative survival rate for patients with NSCLC was higher among women than among men, improving from 35% in 2001 to 44% in 2014.

Improvements in survival were also observed for all races and ethnicities, despite concerns that new cancer treatments might increase treatment disparities between races, because they are all so expensive, the authors commented.

Mortality from SCLC declined by 4.3% a year among men, but that decline was entirely due to a similar decrease in the incidence of SCLC. Survival at 2 years for patients with this subtype of lung cancer remained largely unchanged over the same interval.

Genetic testing

The accelerating decline in NSCLC mortality starting in 2013 corresponds to the period in which clinicians began to routinely test for molecular alterations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), the authors pointed out.

In 2012, the National Comprehensive Cancer Network recommended that all patients with nonsquamous NSCLC undergo genetic testing for EGFR mutations and ALK rearrangements.

At about the same time, the FDA approved a number of targeted therapies for tumors that are sensitive to targeted tyrosine kinase inhibition.

More recently, immunotherapies that act as programmed cell death inhibitors have substantially improved NSCLC outcomes, the authors noted.

The first of these was approved for NSCLC in 2015 (pembrolizumab). It was followed by a number of similar agents. It is unlikely that their approval contributed to the observed decline in NSCLC mortality, which started to accelerate in 2013 in the United States, the authors commented.

Nevertheless, the effect that the immune checkpoint inhibitors has had on the survival of patients with NSCLC can be expected to continue and to extend improvement in survival beyond the current study endpoint in 2016, they suggest.

Another contributing factor is the decline in smoking that has occurred in the United States since the 1960s. This has led to the decrease in the incidence of lung cancer. The faster decrease in the incidence of SCLC, compared with NSCLC can be explained by the higher relative risk of smoking with regard to SCLC compared to NSCLC, they commented.

Similarly, the faster decrease in lung cancer incidence in men compared to women can be explained by the relative difference in the prevalence of smoking between men and women, they added.

The authors disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Mortality from non–small cell lung cancer (NSCLC) has fallen sharply in the United States over the past few years, and survival following its diagnosis has dramatically improved, the first analysis of its kind indicates.

“This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, NSCLC, are declining faster than its incidence, an advance that correlates with the [FDA] approval of several targeted therapies for this cancer in recent years,” coauthor Douglas Lowy, MD, deputy director, National Cancer Institute, Bethesda, Md., said in a statement.

“Major improvements have been made in NSCLC treatment with the advent of targeted therapies and immunotherapies,” lead author Nadia Howlander, PhD, National Cancer Institute, and colleagues observed.

“The survival benefit for patients with NSCLC treated with targeted therapy has been shown in clinical trials, but our study highlights their possible effect at the population level,” they added.

In contrast, mortality from SCLC has dropped only in tandem with a decline in the incidence of SCLC, and survival has remained largely unchanged, the same analysis showed.

NSCLC is by far the most common type of lung cancer, accounting for more than 75% of all lung cancer cases in the United States. SCLC accounts for about 13%.

The study was published online Aug. 12 in the New England Journal of Medicine.

“Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information,” the authors commented.

“To address this data limitation, the U.S. Surveillance, Epidemiology and End Results (SEER) program has linked mortality records to incidence cancer cases,” the authors explained. This allowed them to calculate incidence-based mortality among men and women in the United States.

The incidence-based mortality method that the researchers used was applied to the SEER data to describe population-level mortality trends in the United States that were attributable to each subtype of lung cancer as well as gender from 2001 to 2016.

Among men, the incidence of NSCLC decreased gradually by 1.9% a year from 2001 to 2008, then more dramatically by 3.1% a year from 2008 to 2016.

Corresponding incidence-based mortality rates among men dropped by 3.2% a year from 2006 to 2013, then again more dramatically by 6.3% a year from 2013 to 2016.

“The 2-year relative survival among patients with lung cancer improved substantially from 26% among men with NSCLC diagnosed in 2001 to 35% among those with NSCLC diagnosed in 2014,” the researchers added.

Among women, the incidence of NSCLC remained unchanged between 2001 and 2006, after which it began to drop by 1.5% a year from 2006 to 2016.

“In contrast, incidence-based mortality decreased slowly [among women] by 2.3% annually ... from 2006 through 2014 and then at a faster rate of 5.9% annually ... from 2014 through 2016,” the authors noted.

The 2-year relative survival rate for patients with NSCLC was higher among women than among men, improving from 35% in 2001 to 44% in 2014.

Improvements in survival were also observed for all races and ethnicities, despite concerns that new cancer treatments might increase treatment disparities between races, because they are all so expensive, the authors commented.

Mortality from SCLC declined by 4.3% a year among men, but that decline was entirely due to a similar decrease in the incidence of SCLC. Survival at 2 years for patients with this subtype of lung cancer remained largely unchanged over the same interval.

Genetic testing

The accelerating decline in NSCLC mortality starting in 2013 corresponds to the period in which clinicians began to routinely test for molecular alterations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), the authors pointed out.

In 2012, the National Comprehensive Cancer Network recommended that all patients with nonsquamous NSCLC undergo genetic testing for EGFR mutations and ALK rearrangements.

At about the same time, the FDA approved a number of targeted therapies for tumors that are sensitive to targeted tyrosine kinase inhibition.

More recently, immunotherapies that act as programmed cell death inhibitors have substantially improved NSCLC outcomes, the authors noted.

The first of these was approved for NSCLC in 2015 (pembrolizumab). It was followed by a number of similar agents. It is unlikely that their approval contributed to the observed decline in NSCLC mortality, which started to accelerate in 2013 in the United States, the authors commented.

Nevertheless, the effect that the immune checkpoint inhibitors has had on the survival of patients with NSCLC can be expected to continue and to extend improvement in survival beyond the current study endpoint in 2016, they suggest.

Another contributing factor is the decline in smoking that has occurred in the United States since the 1960s. This has led to the decrease in the incidence of lung cancer. The faster decrease in the incidence of SCLC, compared with NSCLC can be explained by the higher relative risk of smoking with regard to SCLC compared to NSCLC, they commented.

Similarly, the faster decrease in lung cancer incidence in men compared to women can be explained by the relative difference in the prevalence of smoking between men and women, they added.

The authors disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The investigational anti-PD-1 antibody sintilimab (Tyvyt, Innovent Biologics and Eli Lilly) has shown that it improves the efficacy of platinum-based chemotherapy in the first-line treatment of patients with advanced nonsquamous non–small cell lung cancer (NSCLC) in a phase 3 trial dubbed ORIENT-11.

The study was presented at the World Congress on Lung Cancer 2020 Virtual Presidential Symposium, held virtually due to the COVID-19 pandemic, on August 8. It was also published simultaneously in the Journal of Thoracic Oncology.

Sintilimab is a fully human IgG4 monoclonal antibody that blocks the binding of programmed death (PD)-1 to PD-ligand 1 (PD-L1) or PD-L2 with high affinity, and has received market authorization in China for the treatment of Hodgkin lymphoma.

For ORIENT-11, almost 400 patients with advanced nonsquamous NSCLC were randomly assigned to sintilimab or placebo plus pemetrexed and platinum-based chemotherapy in a 2:1 ratio.

“The addition of sintilimab to pemetrexed and platinum significantly improved PFS [progression-free survival], compared to placebo,” reducing progression rates by 52%, noted lead investigator Li Zhang, MD, professor of medical oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Crucially, this benefit “was seen across key clinical subgroups,” he added.

He noted that the overall response rate “was also improved, with a durable response,” while the results, which are not yet mature, suggest the experimental arm was associated with an overall survival (OS) benefit.

Study discussant Misako Nagasaka, MD, a thoracic oncologist and clinical investigator at Karmanos Cancer Institute, Detroit, said that the PFS benefit seen in the study is “certainly encouraging.”

Adding a note of caution, she continued: “But we have seen studies with PFS improvement which did not translate into OS improvement.

“Longer follow-up would allow events to mature and we will ultimately see if there would be a significant OS benefit,” she said.

Dr. Nagasaka also pointed out that the greater benefit with sintilimab seen in patients with high PD-L1 begs the question as to what would be the preferred regimen in those with higher or lower expression.

And, she said, this is not just about what regimen to choose but “more importantly, why?”

“Perhaps you’d like to use something with the best response rate, perhaps you’re sticking to a single agent immunotherapy because the toxicity profile is more favorable, or perhaps you [are] convinced with a certain regimen because of the robust PFS and OS data,” she said.

“Whatever you chose, there was a reason for your choice,” she said, adding that the sintilimab combination would have to “fulfill those reasons for you to consider choosing this regimen.”

Study details

Dr. Zhang began his presentation by noting that previous phase 1b studies have shown that sintilimab plus pemetrexed and platinum-based chemotherapy has a “tolerable safety profile and promising efficacy” in previously untreated non-squamous NSCLC.

They therefore conducted ORIENT-11, a randomized, double-blind, phase 3 study involving 397 patients with untreated stage IIIB/C or IV nonsquamous NSCLC who had neither EGFR nor ALK gene alterations.

The patients were randomly assigned in a 2:1 fashion to sintilimab plus pemetrexed and platinum-based chemotherapy (n = 266) or placebo plus pemetrexed and chemo (n = 131) for four cycles, followed by sintilimab or placebo plus pemetrexed for up to 24 months.

Thirty-five patients in the placebo arm crossed over to sintilimab monotherapy, representing 31.3% of the intention-to-treat population.

At the data cutoff of Nov. 15, 2019, 198 events had occurred, at a median follow-up of 8.9 months.

The team found that median PFS was significantly higher with sintilimab than placebo combination therapy, at 8.9 months vs. 5.0 months, or a hazard ratio of 0.482 (P < .00001).

Dr. Zhang noted that the benefit with sintilimab plus pemetrexed and platinum-based chemotherapy was seen across all subgroups.

However, it was notable that the impact of adding sintilimab on PFS was greater in patients with a tumor proportion score (TPS) ≥50%.

The HR for progression vs. the placebo treatment arm was 0.310, with median PFS not reached, which decreased to 0.503 in patients with a TPS of 1%-49% and 0.664 among those with a TPS <1%.

The results also showed that there was a “nominally significant improvement” in overall survival with sintilimab versus placebo, at a HR of 0.609 (P = 0.01921).

The ORR was markedly different between the sintilimab and placebo groups, at 51.9% vs. 29.8%, with the duration of response not reached in the sintilimab arm compared with 5.5 months in the placebo arm.

The sintilimab arm included three (1.1%) complete responses, which was not observed with pemetrexed and platinum-based chemotherapy alone.

Finally, Dr. Zhang observed that the safety profiles of the sintilimab and placebo arms were similar, with comparable rates of any, grade 3-5, and serious adverse events largely driven by high rates of chemotherapy-related events.

While there were fewer adverse events that led to death with sintilimab, at 2.3% vs. 6.9% with placebo, there were, as expected, more immune-related adverse events, at 43.2% vs. 36.6%, respectively.

Comparison with pembrolizumab

In her discussion, Dr. Nagasaka said that the first question that came to mind when she saw the results was: “How does the ORIENT-11 data compare with KEYNOTE-189?”

For that study, pembrolizumab (Keytruda, Merck) was added to pemetrexed plus carboplatin chemotherapy and compared with standard of care alone in patients with untreated metastatic nonsquamous NSCLC.

As reported by Medscape Medical News, pembrolizumab was associated with a 48% reduced risk of disease progression, as well as improved overall survival.

Dr. Nagasaka said that ORIENT-11 “had patients that tended to be younger, there were more males, more with performance status 1, and those who had never smoked” than those in KEYNOTE-189.

“But most importantly, KEYNOTE-189 had a very small number of patients from East Asia, only 1% in the pembro arm and 2.9% in the placebo arm.”

In contrast, all the patients included in ORIENT-11 were from East Asia, making the study of “high importance.”

She added that, “while across-trial comparisons must be taken with caution, the medium PFS of ORIENT-11 ... appears comparable to those of KEYNOTE-189,” while the HR “appears identical.”

This is despite median follow-up time in ORIENT-11 of “only” 8.9 months vs. a median of 23.1 months in the updated KEYNOTE-189 data.

There are plans to register the sintilimab combination therapy in China for the treatment of nonsquamous NSCLC, where it will go up against pembrolizumab as well as, potentially, tislelizumab (BeiGene).

The study was sponsored by Innovent Biologics and Eli Lilly. Dr. Zhang disclosed research grants from Eli Lilly and Pfizer. Dr. Nagasaka disclosed serving on the advisory boards of AstraZeneca, Daiichi Sankyo, Takeda, Novartis, and EMD Serono; as a consultant for Caris Life Sciences; and receiving travel support from An Hearts Therapeutics.

This article first appeared on Medscape.com.

The investigational anti-PD-1 antibody sintilimab (Tyvyt, Innovent Biologics and Eli Lilly) has shown that it improves the efficacy of platinum-based chemotherapy in the first-line treatment of patients with advanced nonsquamous non–small cell lung cancer (NSCLC) in a phase 3 trial dubbed ORIENT-11.

The study was presented at the World Congress on Lung Cancer 2020 Virtual Presidential Symposium, held virtually due to the COVID-19 pandemic, on August 8. It was also published simultaneously in the Journal of Thoracic Oncology.

Sintilimab is a fully human IgG4 monoclonal antibody that blocks the binding of programmed death (PD)-1 to PD-ligand 1 (PD-L1) or PD-L2 with high affinity, and has received market authorization in China for the treatment of Hodgkin lymphoma.

For ORIENT-11, almost 400 patients with advanced nonsquamous NSCLC were randomly assigned to sintilimab or placebo plus pemetrexed and platinum-based chemotherapy in a 2:1 ratio.

“The addition of sintilimab to pemetrexed and platinum significantly improved PFS [progression-free survival], compared to placebo,” reducing progression rates by 52%, noted lead investigator Li Zhang, MD, professor of medical oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Crucially, this benefit “was seen across key clinical subgroups,” he added.

He noted that the overall response rate “was also improved, with a durable response,” while the results, which are not yet mature, suggest the experimental arm was associated with an overall survival (OS) benefit.

Study discussant Misako Nagasaka, MD, a thoracic oncologist and clinical investigator at Karmanos Cancer Institute, Detroit, said that the PFS benefit seen in the study is “certainly encouraging.”

Adding a note of caution, she continued: “But we have seen studies with PFS improvement which did not translate into OS improvement.

“Longer follow-up would allow events to mature and we will ultimately see if there would be a significant OS benefit,” she said.

Dr. Nagasaka also pointed out that the greater benefit with sintilimab seen in patients with high PD-L1 begs the question as to what would be the preferred regimen in those with higher or lower expression.

And, she said, this is not just about what regimen to choose but “more importantly, why?”

“Perhaps you’d like to use something with the best response rate, perhaps you’re sticking to a single agent immunotherapy because the toxicity profile is more favorable, or perhaps you [are] convinced with a certain regimen because of the robust PFS and OS data,” she said.

“Whatever you chose, there was a reason for your choice,” she said, adding that the sintilimab combination would have to “fulfill those reasons for you to consider choosing this regimen.”

Study details

Dr. Zhang began his presentation by noting that previous phase 1b studies have shown that sintilimab plus pemetrexed and platinum-based chemotherapy has a “tolerable safety profile and promising efficacy” in previously untreated non-squamous NSCLC.

They therefore conducted ORIENT-11, a randomized, double-blind, phase 3 study involving 397 patients with untreated stage IIIB/C or IV nonsquamous NSCLC who had neither EGFR nor ALK gene alterations.

The patients were randomly assigned in a 2:1 fashion to sintilimab plus pemetrexed and platinum-based chemotherapy (n = 266) or placebo plus pemetrexed and chemo (n = 131) for four cycles, followed by sintilimab or placebo plus pemetrexed for up to 24 months.

Thirty-five patients in the placebo arm crossed over to sintilimab monotherapy, representing 31.3% of the intention-to-treat population.

At the data cutoff of Nov. 15, 2019, 198 events had occurred, at a median follow-up of 8.9 months.

The team found that median PFS was significantly higher with sintilimab than placebo combination therapy, at 8.9 months vs. 5.0 months, or a hazard ratio of 0.482 (P < .00001).

Dr. Zhang noted that the benefit with sintilimab plus pemetrexed and platinum-based chemotherapy was seen across all subgroups.

However, it was notable that the impact of adding sintilimab on PFS was greater in patients with a tumor proportion score (TPS) ≥50%.

The HR for progression vs. the placebo treatment arm was 0.310, with median PFS not reached, which decreased to 0.503 in patients with a TPS of 1%-49% and 0.664 among those with a TPS <1%.

The results also showed that there was a “nominally significant improvement” in overall survival with sintilimab versus placebo, at a HR of 0.609 (P = 0.01921).

The ORR was markedly different between the sintilimab and placebo groups, at 51.9% vs. 29.8%, with the duration of response not reached in the sintilimab arm compared with 5.5 months in the placebo arm.

The sintilimab arm included three (1.1%) complete responses, which was not observed with pemetrexed and platinum-based chemotherapy alone.

Finally, Dr. Zhang observed that the safety profiles of the sintilimab and placebo arms were similar, with comparable rates of any, grade 3-5, and serious adverse events largely driven by high rates of chemotherapy-related events.

While there were fewer adverse events that led to death with sintilimab, at 2.3% vs. 6.9% with placebo, there were, as expected, more immune-related adverse events, at 43.2% vs. 36.6%, respectively.

Comparison with pembrolizumab

In her discussion, Dr. Nagasaka said that the first question that came to mind when she saw the results was: “How does the ORIENT-11 data compare with KEYNOTE-189?”

For that study, pembrolizumab (Keytruda, Merck) was added to pemetrexed plus carboplatin chemotherapy and compared with standard of care alone in patients with untreated metastatic nonsquamous NSCLC.

As reported by Medscape Medical News, pembrolizumab was associated with a 48% reduced risk of disease progression, as well as improved overall survival.

Dr. Nagasaka said that ORIENT-11 “had patients that tended to be younger, there were more males, more with performance status 1, and those who had never smoked” than those in KEYNOTE-189.

“But most importantly, KEYNOTE-189 had a very small number of patients from East Asia, only 1% in the pembro arm and 2.9% in the placebo arm.”

In contrast, all the patients included in ORIENT-11 were from East Asia, making the study of “high importance.”

She added that, “while across-trial comparisons must be taken with caution, the medium PFS of ORIENT-11 ... appears comparable to those of KEYNOTE-189,” while the HR “appears identical.”

This is despite median follow-up time in ORIENT-11 of “only” 8.9 months vs. a median of 23.1 months in the updated KEYNOTE-189 data.

There are plans to register the sintilimab combination therapy in China for the treatment of nonsquamous NSCLC, where it will go up against pembrolizumab as well as, potentially, tislelizumab (BeiGene).

The study was sponsored by Innovent Biologics and Eli Lilly. Dr. Zhang disclosed research grants from Eli Lilly and Pfizer. Dr. Nagasaka disclosed serving on the advisory boards of AstraZeneca, Daiichi Sankyo, Takeda, Novartis, and EMD Serono; as a consultant for Caris Life Sciences; and receiving travel support from An Hearts Therapeutics.

This article first appeared on Medscape.com.

The investigational anti-PD-1 antibody sintilimab (Tyvyt, Innovent Biologics and Eli Lilly) has shown that it improves the efficacy of platinum-based chemotherapy in the first-line treatment of patients with advanced nonsquamous non–small cell lung cancer (NSCLC) in a phase 3 trial dubbed ORIENT-11.

The study was presented at the World Congress on Lung Cancer 2020 Virtual Presidential Symposium, held virtually due to the COVID-19 pandemic, on August 8. It was also published simultaneously in the Journal of Thoracic Oncology.

Sintilimab is a fully human IgG4 monoclonal antibody that blocks the binding of programmed death (PD)-1 to PD-ligand 1 (PD-L1) or PD-L2 with high affinity, and has received market authorization in China for the treatment of Hodgkin lymphoma.

For ORIENT-11, almost 400 patients with advanced nonsquamous NSCLC were randomly assigned to sintilimab or placebo plus pemetrexed and platinum-based chemotherapy in a 2:1 ratio.

“The addition of sintilimab to pemetrexed and platinum significantly improved PFS [progression-free survival], compared to placebo,” reducing progression rates by 52%, noted lead investigator Li Zhang, MD, professor of medical oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Crucially, this benefit “was seen across key clinical subgroups,” he added.

He noted that the overall response rate “was also improved, with a durable response,” while the results, which are not yet mature, suggest the experimental arm was associated with an overall survival (OS) benefit.

Study discussant Misako Nagasaka, MD, a thoracic oncologist and clinical investigator at Karmanos Cancer Institute, Detroit, said that the PFS benefit seen in the study is “certainly encouraging.”

Adding a note of caution, she continued: “But we have seen studies with PFS improvement which did not translate into OS improvement.

“Longer follow-up would allow events to mature and we will ultimately see if there would be a significant OS benefit,” she said.

Dr. Nagasaka also pointed out that the greater benefit with sintilimab seen in patients with high PD-L1 begs the question as to what would be the preferred regimen in those with higher or lower expression.

And, she said, this is not just about what regimen to choose but “more importantly, why?”

“Perhaps you’d like to use something with the best response rate, perhaps you’re sticking to a single agent immunotherapy because the toxicity profile is more favorable, or perhaps you [are] convinced with a certain regimen because of the robust PFS and OS data,” she said.

“Whatever you chose, there was a reason for your choice,” she said, adding that the sintilimab combination would have to “fulfill those reasons for you to consider choosing this regimen.”

Study details

Dr. Zhang began his presentation by noting that previous phase 1b studies have shown that sintilimab plus pemetrexed and platinum-based chemotherapy has a “tolerable safety profile and promising efficacy” in previously untreated non-squamous NSCLC.

They therefore conducted ORIENT-11, a randomized, double-blind, phase 3 study involving 397 patients with untreated stage IIIB/C or IV nonsquamous NSCLC who had neither EGFR nor ALK gene alterations.

The patients were randomly assigned in a 2:1 fashion to sintilimab plus pemetrexed and platinum-based chemotherapy (n = 266) or placebo plus pemetrexed and chemo (n = 131) for four cycles, followed by sintilimab or placebo plus pemetrexed for up to 24 months.

Thirty-five patients in the placebo arm crossed over to sintilimab monotherapy, representing 31.3% of the intention-to-treat population.

At the data cutoff of Nov. 15, 2019, 198 events had occurred, at a median follow-up of 8.9 months.

The team found that median PFS was significantly higher with sintilimab than placebo combination therapy, at 8.9 months vs. 5.0 months, or a hazard ratio of 0.482 (P < .00001).

Dr. Zhang noted that the benefit with sintilimab plus pemetrexed and platinum-based chemotherapy was seen across all subgroups.

However, it was notable that the impact of adding sintilimab on PFS was greater in patients with a tumor proportion score (TPS) ≥50%.

The HR for progression vs. the placebo treatment arm was 0.310, with median PFS not reached, which decreased to 0.503 in patients with a TPS of 1%-49% and 0.664 among those with a TPS <1%.

The results also showed that there was a “nominally significant improvement” in overall survival with sintilimab versus placebo, at a HR of 0.609 (P = 0.01921).

The ORR was markedly different between the sintilimab and placebo groups, at 51.9% vs. 29.8%, with the duration of response not reached in the sintilimab arm compared with 5.5 months in the placebo arm.

The sintilimab arm included three (1.1%) complete responses, which was not observed with pemetrexed and platinum-based chemotherapy alone.

Finally, Dr. Zhang observed that the safety profiles of the sintilimab and placebo arms were similar, with comparable rates of any, grade 3-5, and serious adverse events largely driven by high rates of chemotherapy-related events.

While there were fewer adverse events that led to death with sintilimab, at 2.3% vs. 6.9% with placebo, there were, as expected, more immune-related adverse events, at 43.2% vs. 36.6%, respectively.

Comparison with pembrolizumab

In her discussion, Dr. Nagasaka said that the first question that came to mind when she saw the results was: “How does the ORIENT-11 data compare with KEYNOTE-189?”

For that study, pembrolizumab (Keytruda, Merck) was added to pemetrexed plus carboplatin chemotherapy and compared with standard of care alone in patients with untreated metastatic nonsquamous NSCLC.

As reported by Medscape Medical News, pembrolizumab was associated with a 48% reduced risk of disease progression, as well as improved overall survival.

Dr. Nagasaka said that ORIENT-11 “had patients that tended to be younger, there were more males, more with performance status 1, and those who had never smoked” than those in KEYNOTE-189.

“But most importantly, KEYNOTE-189 had a very small number of patients from East Asia, only 1% in the pembro arm and 2.9% in the placebo arm.”

In contrast, all the patients included in ORIENT-11 were from East Asia, making the study of “high importance.”

She added that, “while across-trial comparisons must be taken with caution, the medium PFS of ORIENT-11 ... appears comparable to those of KEYNOTE-189,” while the HR “appears identical.”

This is despite median follow-up time in ORIENT-11 of “only” 8.9 months vs. a median of 23.1 months in the updated KEYNOTE-189 data.

There are plans to register the sintilimab combination therapy in China for the treatment of nonsquamous NSCLC, where it will go up against pembrolizumab as well as, potentially, tislelizumab (BeiGene).

The study was sponsored by Innovent Biologics and Eli Lilly. Dr. Zhang disclosed research grants from Eli Lilly and Pfizer. Dr. Nagasaka disclosed serving on the advisory boards of AstraZeneca, Daiichi Sankyo, Takeda, Novartis, and EMD Serono; as a consultant for Caris Life Sciences; and receiving travel support from An Hearts Therapeutics.

This article first appeared on Medscape.com.

Patients with untreated mesothelioma may be able to avoid chemotherapy, say researchers reporting new survival data with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy).

The two approaches were compared in more than 600 patients with treatment-naive mesothelioma in the phase 3 CheckMate 743 trial, which was supported by the manufacturer of both immunotherapies, Bristol-Myers Squibb.

The trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported Paul Baas, MD, PhD, Netherlands Cancer Institute, Amsterdam, The Netherlands,

The combined nivo+ipi immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive, vs 27% in the chemotherapy group.

“This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma,” he said. He suggested that it should therefore “be considered as a new standard of care.”

The data were presented on August 8 in the presidential symposium of the World Congress on Lung Cancer 2020, which was held online because of the COVID-19 pandemic.

A key analysis for the study was by histologic subgroup. It is known that standard-of-care chemotherapy performs better in patients with epithelioid as opposed to nonepithelioid tumor subtypes.

Bass highlighted that the performance of nivo+ipi was “almost the same” in patients with epithelioid and nonepithelioid tumors, at a median overall survival of 18.7 months and 18.1 months, respectively.

In contrast, overall survival in the chemotherapy arm was markedly lower in patients with nonepithelioid tumors, at 8.8 months vs 16.5 months among those with epithelioid tumors.

This was reflected in the hazard ratios for overall survival vs nivo+ipi, at 0.46 and 0.86, respectively, the latter nonsignificantly different from combination immunotherapy.

For study discussant Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester, United Kingdom, the epithet of a “new standard of care” for nivo+ipi should be reserved for nonepithelioid disease.

In this setting, he described the overall survival improvement as “transformative,” considering the “marked chemo resistance” of nonepithelioid tumors, which is “almost certainly” associated with epithelial-to-mesenchymal transition (EMT).

In the future, he suggested, combinations of chemotherapy and immunotherapy involving all histologies or selective targeting of nonepithelioid mesothelioma “could further extend the benefit for patients.”
 

Improving survival in mesothelioma

“We have been trying to improve the overall survival of patients with mesothelioma now for many decades,” Bass commented. Platinum-based chemotherapy plus pemetrexed is a standard of care, although the 5-year survival rate «is still below 10%,” he noted.

Randomized trials of single-agent immune checkpoint inhibitor therapy in the second-line treatment of patients with mesothelioma have not shown any significant benefits.

However, nivolumab and ipilimumab have a “complementary mechanism of action,” and two previous reports have indicated that together, they have clinical activity in the second-line setting.

The team conducted CheckMate 743 to determine the efficacy of the combination in the first-line setting.

The study involved 605 patients with pleural mesothelioma who had received no prior systemic therapy and had good performance status.

They were randomly assigned in a 1:1 ratio to receive nivo+ipi for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin until disease progression or unacceptable toxicity occurred.

“Patients could have a subsequent therapy,” Bass noted; 44.0% of patients in the experimental arm received subsequent therapy, vs 44.1% of those in the chemotherapy arm.

Of the latter, 20% received an immune checkpoint inhibitor as subsequent therapy.

The minimum follow-up for overall survival was 22.1 months; the median follow-up was 29.7 months.

Nivo+ipi was associated with a significant improvement in overall survival vs standard-of-care chemotherapy, at a median overall survival of 18.1 months vs 14.1 months, with a hazard ratio of 0.74 (P = .0020).

The results indicated that overall survival was similar across key subgroups, which suggests that “no subgroup was harmed” by nivo+ipi, Bass said.
 

Stratification by PD-LI expression

Stratifying the patients by the absence or presence of programmed cell death–ligand-1 (PD-L1) expression, the team found that the performance of nivo+ipi was “the same” as that of chemotherapy, Bass said.

“But in cases where there is any expression of PD-L1, the experimental arm performs better,” at an overall survival 18.0 months vs 13.3 months for chemotherapy and a hazard ratio of 0.69, he said.

There was no difference between the two treatment arms in progression-free survival. Chemotherapy performed better in the first 6 months of treatment, after which the nivo+ipi arm had lower event rates.

Nivo+ipi was also associated with a greater duration of response, at a median of 11.0 months vs 6.7 months for standard-of-care chemotherapy.

Moreover, at 24 months, 32% of nivo+ipi patients were still experiencing a response, whereas 8% of those in the chemotherapy arm were.

Treatment-related adverse events rates were almost identical between the two treatment groups, although treatment with nivo+ipi was associated with more grade 3/4 serious treatment-related adverse events, at 15 vs six for chemotherapy.
 

Choosing immunotherapy vs. chemotherapy

In his discussion of the new study, Fennell compared the current results with those from two studies, INITIATE and MAPS2. “What’s very clear is the response rate is slightly higher,” as is the disease control rate, he said.

This, he explained, “is perhaps not surprising, given that these two previous trials were in the relapse setting.”

He pointed out, however, that the progression-free survival data from those previous trials were “not a million miles away” from results seen in CheckMate 743, “suggesting that this immunotherapy does have significant activity in the relapse setting.”

For Fennell, the “pivotal data” are in patients with nonepithelioid tumors, particularly inasmuch as chemotherapy performed “poorly” in this setting, whereas it performs “as expected” in epithelioid mesothelioma.

He believes that the driver for this is the poor prognosis associated with sarcomatoid biphasic disease, a subtype characterized by increased expression of vimentin and ZEB1, proteins both associated with EMT.

“What does this mean?” Fennell asked.

“If you have have enrichment of EMT, what you see is increased drug resistance, increased invasiveness, something we know well with sarcomatoid mesotheliomas in particular, and this drug-resistance phenotype may account for the drug resistance that we see in CheckMate 743 with chemotherapy.

“This does not appear, however, to impact in any way the efficacy of the immunotherapy,” he noted.

Fennell believes that, with regard to both efficacy and safety, the balance is “very much in favor” of nivo+ipi in epithelioid mesothelioma, although there is less to choose between immunotherapy and chemotherapy in the nonepithelioid setting.

Indeed, the choice is “possible tilting slightly towards chemotherapy” in patients with the nonepithelioid tumors, owing to the lower rates of grade 3/4 serious treatment-related adverse events in comparison with combination immunotherapy.

The study was supported by Bristol-Myers Squibb. Bass has served on the advisory boards of MSD, AstraZeneca, and Takeda. Fennell has received research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, MSD, and Roche; research funding from Astex Therapeutics, Bayer, and Boehringer Ingelheim; has served on the speaker bureau of AstraZeneca, Boehringer Ingelheim, and Roche; has acted as a consultant for Bayer and Lab 21; and has served on the advisory board of Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.

This article first appeared on Medscape.com.

Patients with untreated mesothelioma may be able to avoid chemotherapy, say researchers reporting new survival data with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy).

The two approaches were compared in more than 600 patients with treatment-naive mesothelioma in the phase 3 CheckMate 743 trial, which was supported by the manufacturer of both immunotherapies, Bristol-Myers Squibb.

The trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported Paul Baas, MD, PhD, Netherlands Cancer Institute, Amsterdam, The Netherlands,

The combined nivo+ipi immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive, vs 27% in the chemotherapy group.

“This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma,” he said. He suggested that it should therefore “be considered as a new standard of care.”

The data were presented on August 8 in the presidential symposium of the World Congress on Lung Cancer 2020, which was held online because of the COVID-19 pandemic.

A key analysis for the study was by histologic subgroup. It is known that standard-of-care chemotherapy performs better in patients with epithelioid as opposed to nonepithelioid tumor subtypes.

Bass highlighted that the performance of nivo+ipi was “almost the same” in patients with epithelioid and nonepithelioid tumors, at a median overall survival of 18.7 months and 18.1 months, respectively.

In contrast, overall survival in the chemotherapy arm was markedly lower in patients with nonepithelioid tumors, at 8.8 months vs 16.5 months among those with epithelioid tumors.

This was reflected in the hazard ratios for overall survival vs nivo+ipi, at 0.46 and 0.86, respectively, the latter nonsignificantly different from combination immunotherapy.

For study discussant Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester, United Kingdom, the epithet of a “new standard of care” for nivo+ipi should be reserved for nonepithelioid disease.

In this setting, he described the overall survival improvement as “transformative,” considering the “marked chemo resistance” of nonepithelioid tumors, which is “almost certainly” associated with epithelial-to-mesenchymal transition (EMT).

In the future, he suggested, combinations of chemotherapy and immunotherapy involving all histologies or selective targeting of nonepithelioid mesothelioma “could further extend the benefit for patients.”
 

Improving survival in mesothelioma

“We have been trying to improve the overall survival of patients with mesothelioma now for many decades,” Bass commented. Platinum-based chemotherapy plus pemetrexed is a standard of care, although the 5-year survival rate «is still below 10%,” he noted.

Randomized trials of single-agent immune checkpoint inhibitor therapy in the second-line treatment of patients with mesothelioma have not shown any significant benefits.

However, nivolumab and ipilimumab have a “complementary mechanism of action,” and two previous reports have indicated that together, they have clinical activity in the second-line setting.

The team conducted CheckMate 743 to determine the efficacy of the combination in the first-line setting.

The study involved 605 patients with pleural mesothelioma who had received no prior systemic therapy and had good performance status.

They were randomly assigned in a 1:1 ratio to receive nivo+ipi for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin until disease progression or unacceptable toxicity occurred.

“Patients could have a subsequent therapy,” Bass noted; 44.0% of patients in the experimental arm received subsequent therapy, vs 44.1% of those in the chemotherapy arm.

Of the latter, 20% received an immune checkpoint inhibitor as subsequent therapy.

The minimum follow-up for overall survival was 22.1 months; the median follow-up was 29.7 months.

Nivo+ipi was associated with a significant improvement in overall survival vs standard-of-care chemotherapy, at a median overall survival of 18.1 months vs 14.1 months, with a hazard ratio of 0.74 (P = .0020).

The results indicated that overall survival was similar across key subgroups, which suggests that “no subgroup was harmed” by nivo+ipi, Bass said.
 

Stratification by PD-LI expression

Stratifying the patients by the absence or presence of programmed cell death–ligand-1 (PD-L1) expression, the team found that the performance of nivo+ipi was “the same” as that of chemotherapy, Bass said.

“But in cases where there is any expression of PD-L1, the experimental arm performs better,” at an overall survival 18.0 months vs 13.3 months for chemotherapy and a hazard ratio of 0.69, he said.

There was no difference between the two treatment arms in progression-free survival. Chemotherapy performed better in the first 6 months of treatment, after which the nivo+ipi arm had lower event rates.

Nivo+ipi was also associated with a greater duration of response, at a median of 11.0 months vs 6.7 months for standard-of-care chemotherapy.

Moreover, at 24 months, 32% of nivo+ipi patients were still experiencing a response, whereas 8% of those in the chemotherapy arm were.

Treatment-related adverse events rates were almost identical between the two treatment groups, although treatment with nivo+ipi was associated with more grade 3/4 serious treatment-related adverse events, at 15 vs six for chemotherapy.
 

Choosing immunotherapy vs. chemotherapy

In his discussion of the new study, Fennell compared the current results with those from two studies, INITIATE and MAPS2. “What’s very clear is the response rate is slightly higher,” as is the disease control rate, he said.

This, he explained, “is perhaps not surprising, given that these two previous trials were in the relapse setting.”

He pointed out, however, that the progression-free survival data from those previous trials were “not a million miles away” from results seen in CheckMate 743, “suggesting that this immunotherapy does have significant activity in the relapse setting.”

For Fennell, the “pivotal data” are in patients with nonepithelioid tumors, particularly inasmuch as chemotherapy performed “poorly” in this setting, whereas it performs “as expected” in epithelioid mesothelioma.

He believes that the driver for this is the poor prognosis associated with sarcomatoid biphasic disease, a subtype characterized by increased expression of vimentin and ZEB1, proteins both associated with EMT.

“What does this mean?” Fennell asked.

“If you have have enrichment of EMT, what you see is increased drug resistance, increased invasiveness, something we know well with sarcomatoid mesotheliomas in particular, and this drug-resistance phenotype may account for the drug resistance that we see in CheckMate 743 with chemotherapy.

“This does not appear, however, to impact in any way the efficacy of the immunotherapy,” he noted.

Fennell believes that, with regard to both efficacy and safety, the balance is “very much in favor” of nivo+ipi in epithelioid mesothelioma, although there is less to choose between immunotherapy and chemotherapy in the nonepithelioid setting.

Indeed, the choice is “possible tilting slightly towards chemotherapy” in patients with the nonepithelioid tumors, owing to the lower rates of grade 3/4 serious treatment-related adverse events in comparison with combination immunotherapy.

The study was supported by Bristol-Myers Squibb. Bass has served on the advisory boards of MSD, AstraZeneca, and Takeda. Fennell has received research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, MSD, and Roche; research funding from Astex Therapeutics, Bayer, and Boehringer Ingelheim; has served on the speaker bureau of AstraZeneca, Boehringer Ingelheim, and Roche; has acted as a consultant for Bayer and Lab 21; and has served on the advisory board of Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.

This article first appeared on Medscape.com.

Patients with untreated mesothelioma may be able to avoid chemotherapy, say researchers reporting new survival data with the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy).

The two approaches were compared in more than 600 patients with treatment-naive mesothelioma in the phase 3 CheckMate 743 trial, which was supported by the manufacturer of both immunotherapies, Bristol-Myers Squibb.

The trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported Paul Baas, MD, PhD, Netherlands Cancer Institute, Amsterdam, The Netherlands,

The combined nivo+ipi immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive, vs 27% in the chemotherapy group.

“This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma,” he said. He suggested that it should therefore “be considered as a new standard of care.”

The data were presented on August 8 in the presidential symposium of the World Congress on Lung Cancer 2020, which was held online because of the COVID-19 pandemic.

A key analysis for the study was by histologic subgroup. It is known that standard-of-care chemotherapy performs better in patients with epithelioid as opposed to nonepithelioid tumor subtypes.

Bass highlighted that the performance of nivo+ipi was “almost the same” in patients with epithelioid and nonepithelioid tumors, at a median overall survival of 18.7 months and 18.1 months, respectively.

In contrast, overall survival in the chemotherapy arm was markedly lower in patients with nonepithelioid tumors, at 8.8 months vs 16.5 months among those with epithelioid tumors.

This was reflected in the hazard ratios for overall survival vs nivo+ipi, at 0.46 and 0.86, respectively, the latter nonsignificantly different from combination immunotherapy.

For study discussant Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester, United Kingdom, the epithet of a “new standard of care” for nivo+ipi should be reserved for nonepithelioid disease.

In this setting, he described the overall survival improvement as “transformative,” considering the “marked chemo resistance” of nonepithelioid tumors, which is “almost certainly” associated with epithelial-to-mesenchymal transition (EMT).

In the future, he suggested, combinations of chemotherapy and immunotherapy involving all histologies or selective targeting of nonepithelioid mesothelioma “could further extend the benefit for patients.”
 

Improving survival in mesothelioma

“We have been trying to improve the overall survival of patients with mesothelioma now for many decades,” Bass commented. Platinum-based chemotherapy plus pemetrexed is a standard of care, although the 5-year survival rate «is still below 10%,” he noted.

Randomized trials of single-agent immune checkpoint inhibitor therapy in the second-line treatment of patients with mesothelioma have not shown any significant benefits.

However, nivolumab and ipilimumab have a “complementary mechanism of action,” and two previous reports have indicated that together, they have clinical activity in the second-line setting.

The team conducted CheckMate 743 to determine the efficacy of the combination in the first-line setting.

The study involved 605 patients with pleural mesothelioma who had received no prior systemic therapy and had good performance status.

They were randomly assigned in a 1:1 ratio to receive nivo+ipi for up to 2 years or six cycles of pemetrexed plus cisplatin or carboplatin until disease progression or unacceptable toxicity occurred.

“Patients could have a subsequent therapy,” Bass noted; 44.0% of patients in the experimental arm received subsequent therapy, vs 44.1% of those in the chemotherapy arm.

Of the latter, 20% received an immune checkpoint inhibitor as subsequent therapy.

The minimum follow-up for overall survival was 22.1 months; the median follow-up was 29.7 months.

Nivo+ipi was associated with a significant improvement in overall survival vs standard-of-care chemotherapy, at a median overall survival of 18.1 months vs 14.1 months, with a hazard ratio of 0.74 (P = .0020).

The results indicated that overall survival was similar across key subgroups, which suggests that “no subgroup was harmed” by nivo+ipi, Bass said.
 

Stratification by PD-LI expression

Stratifying the patients by the absence or presence of programmed cell death–ligand-1 (PD-L1) expression, the team found that the performance of nivo+ipi was “the same” as that of chemotherapy, Bass said.

“But in cases where there is any expression of PD-L1, the experimental arm performs better,” at an overall survival 18.0 months vs 13.3 months for chemotherapy and a hazard ratio of 0.69, he said.

There was no difference between the two treatment arms in progression-free survival. Chemotherapy performed better in the first 6 months of treatment, after which the nivo+ipi arm had lower event rates.

Nivo+ipi was also associated with a greater duration of response, at a median of 11.0 months vs 6.7 months for standard-of-care chemotherapy.

Moreover, at 24 months, 32% of nivo+ipi patients were still experiencing a response, whereas 8% of those in the chemotherapy arm were.

Treatment-related adverse events rates were almost identical between the two treatment groups, although treatment with nivo+ipi was associated with more grade 3/4 serious treatment-related adverse events, at 15 vs six for chemotherapy.
 

Choosing immunotherapy vs. chemotherapy

In his discussion of the new study, Fennell compared the current results with those from two studies, INITIATE and MAPS2. “What’s very clear is the response rate is slightly higher,” as is the disease control rate, he said.

This, he explained, “is perhaps not surprising, given that these two previous trials were in the relapse setting.”

He pointed out, however, that the progression-free survival data from those previous trials were “not a million miles away” from results seen in CheckMate 743, “suggesting that this immunotherapy does have significant activity in the relapse setting.”

For Fennell, the “pivotal data” are in patients with nonepithelioid tumors, particularly inasmuch as chemotherapy performed “poorly” in this setting, whereas it performs “as expected” in epithelioid mesothelioma.

He believes that the driver for this is the poor prognosis associated with sarcomatoid biphasic disease, a subtype characterized by increased expression of vimentin and ZEB1, proteins both associated with EMT.

“What does this mean?” Fennell asked.

“If you have have enrichment of EMT, what you see is increased drug resistance, increased invasiveness, something we know well with sarcomatoid mesotheliomas in particular, and this drug-resistance phenotype may account for the drug resistance that we see in CheckMate 743 with chemotherapy.

“This does not appear, however, to impact in any way the efficacy of the immunotherapy,” he noted.

Fennell believes that, with regard to both efficacy and safety, the balance is “very much in favor” of nivo+ipi in epithelioid mesothelioma, although there is less to choose between immunotherapy and chemotherapy in the nonepithelioid setting.

Indeed, the choice is “possible tilting slightly towards chemotherapy” in patients with the nonepithelioid tumors, owing to the lower rates of grade 3/4 serious treatment-related adverse events in comparison with combination immunotherapy.

The study was supported by Bristol-Myers Squibb. Bass has served on the advisory boards of MSD, AstraZeneca, and Takeda. Fennell has received research support from AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, MSD, and Roche; research funding from Astex Therapeutics, Bayer, and Boehringer Ingelheim; has served on the speaker bureau of AstraZeneca, Boehringer Ingelheim, and Roche; has acted as a consultant for Bayer and Lab 21; and has served on the advisory board of Atara Biotherapeutics, Boehringer Ingelheim, and Inventiva.

This article first appeared on Medscape.com.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

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.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

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.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

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.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

Immune checkpoint inhibition was not associated with an increased mortality risk from COVID-19 in patients with cancer in an international observational study.

The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.

In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.

“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.

COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.

He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
 

Study details

Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.

The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).

The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.

Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.

Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.

Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.

At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.

Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.

Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.

At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
 

Mortality results

Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.

“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”

Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.

The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.

“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.

Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.

Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.

Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.

“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.

Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.

sworcester@mdedge.com

SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.

Immune checkpoint inhibition was not associated with an increased mortality risk from COVID-19 in patients with cancer in an international observational study.

The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.

In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.

“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.

COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.

He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
 

Study details

Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.

The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).

The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.

Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.

Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.

Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.

At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.

Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.

Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.

At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
 

Mortality results

Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.

“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”

Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.

The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.

“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.

Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.

Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.

Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.

“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.

Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.

sworcester@mdedge.com

SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.

Immune checkpoint inhibition was not associated with an increased mortality risk from COVID-19 in patients with cancer in an international observational study.

The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.

In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.

“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.

COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.

He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
 

Study details

Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.

The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).

The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.

Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.

Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.

Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.

At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.

Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.

Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.

At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
 

Mortality results

Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.

“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”

Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.

The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.

“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.

Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.

Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.

Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.

“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.

Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.

sworcester@mdedge.com

SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

The American Society of Clinical Oncology “does not generally support” at-home infusions of anticancer therapy because of safety concerns, the organization says in a new policy statement issued July 31.

At the same time, it supports exceptions: namely, when individual physicians and patients, having jointly discussed risks and benefits, agree to have treatments administered in the home.

The new policy is limited to intravenous infusions of anticancer agents such as chemotherapy, monoclonal antibodies, and other drugs — administered by health care personnel. It does not refer to injections.

The policy was prompted by regulatory flexibilities from the Centers for Medicare & Medicaid Services made in response to the accelerating COVID-19 pandemic. “Among these flexibilities were new provisions that enabled providers to deliver care in a setting most appropriate – and safest – for individual patient circumstances,” which has “opened the path for potential increases in use of home infusion for anticancer therapy,” says ASCO.

“We’re not ready to endorse [chemo at home] as a general policy until we have evidence that it’s safe. At the same time, the policy gives physicians and patients autonomy to respond to whatever situation they find themselves in,” Stephen Grubbs, MD, ASCO’s senior director of clinical affairs, said in an interview.

“Antineoplastic drugs are effective at treating cancer but can be extremely toxic to normal human cells,” reads the statement, which was written by a group of about 25 professionals, including Grubbs and other ASCO staff as well as independent advisers.

“There is a paucity of evidence directly comparing the safety of chemotherapy infusions in the home and outpatient settings,” the ASCO policy explains.

ASCO’s policy acknowledges that there are data “from other countries demonstrating that ... home infusion can be safe, well-tolerated, and may be preferred by some patients.” But such data are limited and only apply “to certain circumstances and for specific agents,” it adds.

One US cancer center (in Philadelphia) already has an established chemo-at-home program and has seen an increase in its use during the pandemic, as reported by Medscape Medical News. Approached for comment, Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation in Philadelphia, interpreted the new ASCO policy in a positive light.

“Physicians at the Abramson Cancer Center of the University of Pennsylvania and ASCO agree – home-based cancer therapy with oncologist oversight and well-designed safety protocols can be a safe option for patients with cancer,” he said in a statement.

ASCO says its existing safety standards “may be difficult to satisfy in the home infusion context,” including for safely resolving life-threatening emergencies.

Grubbs said that in the worst-case scenario, such as anaphylaxis, “you can die from [it] if you don’t manage it quickly and properly.”

“When I was practicing, we always had a physician present right next to the infusion area because these are severe reactions that happen very quickly,” he said, adding that “several a year” occurred when he practiced full-time.

Also, chemotherapy spills are a “big deal” in the home, as clean-up may be complex and difficult, added Grubbs.

Data from ASCO’s PracticeNET program show that in the first months (March and April) of the COVID-19 pandemic, chemotherapy visits to infusion suites were not reduced in a dataset of 16 US practices, he noted. However, there are exceptions and variance based on location, Grubbs said, such as “hot spots” including New York City in April.

While the pandemic has no end in sight, ASCO issued a set of six recommendations for use of anticancer therapies infused in the home. First, they call for independent, publicly funded research to evaluate the safety and effectiveness of home infusion of anticancer therapy.

Next in importance, ASCO wants the current temporary regulation change from CMS due to the pandemic to end.

“CMS should not extend the temporary flexibility related to home infusion for Part B cancer drugs that was approved as part of their response to the public health emergency,” they state.

Even before the pandemic, changes were afoot. Under the 21st Century Cures Act, which was passed in 2019 and will be implemented in 2021, CMS instituted a permanent home infusion therapy services benefit, which includes anticancer therapies. It “remains to be seen what, if any, shift away from outpatient infusion facilities will occur,” observes ASCO in its policy statement.

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.