Mark L. Fuerst

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

Women who receive ovarian stimulation for assisted reproductive technology (ART) procedures don’t have an increased risk of developing ovarian cancer when compared to subfertile women who don’t undergo ART, according to a new study.

The results suggest that nulliparity is likely responsible for the increased risk of ovarian cancer observed in patients treated with ART, the researchers said.

Earlier, shorter studies had only compared ART-treated women with women from the general population.

“Subfertile women differ from women in the general population according to several ovarian cancer risk factors. Therefore, to estimate the risk of ovarian cancer associated with ART, it was important to include a comparison group of women who were subfertile and not treated with ART,” said senior study author Flora E. van Leeuwen, PhD, of Netherlands Cancer Institute in Amsterdam.

She and her colleagues conducted a nationwide cohort study of 30,625 women who received ovarian stimulation for ART during 1983-2000 and 9,988 women who received fertility treatments other than ART.

Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group.

The researchers reported the results in the Journal of the National Cancer Institute.
 

Risk of ovarian cancer

Women treated with ART were no more likely to develop ovarian cancer than subfertile women not treated with ART (adjusted hazard ratio, 1.02), but the ART group did have an increased risk of ovarian cancer when compared to the general population (standardized incidence ratio, 1.43).

“This, however, turned out to be due to the fact that the women who had received ART were less likely to have children. Not having children is a known risk factor for ovarian cancer,” Dr. van Leeuwen said.

Women with more ART procedures that resulted in the birth of a child were at lower risk of developing ovarian cancer, compared with women without any successful cycle (Ptrend = .001). However, women who had only cycles not resulting in a birth were not at higher risk of ovarian cancer when they had a greater number of cycles.

“These results indicate that parity decreases the risk of ovarian cancer, also in ART-treated women. But more unsuccessful ART cycles do not increase the risk of ovarian cancer,” Dr. van Leeuwen said.
 

Risk of borderline ovarian tumors

The risk of developing borderline ovarian tumors was roughly twice as high in women who had received ART, both compared with women who had received other fertility treatments (hazard ratio, 1.84) and women from the general population (standardized incidence ratio, 2.20).

However, the risk of developing borderline ovarian tumors did not increase in women who had received multiple ART procedures.

“If there was a causal association between ART and increased risk of borderline ovarian tumors, we would expect to see this risk increase with a greater number of ART procedures from more hormones and more stimulation of the ovaries. This makes the direct link between ART and increased risk of borderline tumors a bit uncertain. It might be caused by other factors, such as the severity of infertility,” Dr. van Leeuwen said.

Borderline ovarian tumors are rare in the general population in the Netherlands, and women who develop these tumors generally have a good prognosis, she said.

The risk of developing a borderline tumor before the age of 55 for women in the Netherlands is approximately 0.2%. After ART, the study found a risk of approximately 0.3%.

Causal associations with ART 'unlikely'

“Women who develop cancer and have undergone ART procedures in the past may wonder whether their cancer may be caused by ART. Based on the results from our study, that seems unlikely, and that is a very reassuring message from practicing oncologists to women diagnosed with ovarian cancer. Another important message is that, in ART-treated women, increasing parity reduces the risk of ovarian cancer,” Dr. van Leeuwen said.

She added that the risk of borderline ovarian tumors did not increase in women who received multiple ART procedures, “which makes it somewhat less likely that ART would have caused their borderline ovarian tumor.”

The study does not exclude the possibility that ART might increase the risk of ovarian tumors after age 60.

“Despite our long follow-up, the age of the women at the end of our study was still relatively young [average 56 years]. Because the incidence of ovarian cancer increases with older age, it is vital to continue to follow these women. Only then can we be sure that ART does not increase the risk of ovarian tumors in the very long run,” Dr. van Leeuwen said.

“This study offers confirmation of several previous studies and provides reassurance about the risk of ovarian cancer after ART procedures,” said Daniel Kenigsberg, MD, of RMA Long Island IVF in New York. Dr. Kenigsberg was not involved in this study but has performed more than 30,000 ART procedures over the past 32 years.

“Researchers have looked at whether fertility drugs cause ovarian cancer in different ways and in different countries, and there is no cause-and-effect relationship. There was no dose-response relationship between ART and ovarian tumors in this study. It’s more likely there is something wrong with the women’s ovaries that lead to borderline tumors and infertility more than any treatment,” Dr. Kenigsberg added.

“Perhaps both fertility and cancer relate to an underlying ovarian issue, but this would not explain the increased cancer incidence in those who never attempted pregnancy, that is, women who are voluntarily childless. Pregnancy is statistically protective: more pregnancies lead to less ovarian cancer, but this is far from absolute,” he explained.

Dr. Kenigsberg suggested that oncologists should be aware of a patient’s obstetrical history and fertility history as well as any related medical interventions.

“Borderline tumors look like cancer and have histologic features of cancer but do not meet the criteria for a cancer diagnosis,” he said. “They require close surveillance because their relationship to the development of full-fledged cancer is uncertain.”

This research was supported by grants from the Dutch Cancer Society. The authors and Dr. Kenigsberg have no conflicts of interest.

Women who receive ovarian stimulation for assisted reproductive technology (ART) procedures don’t have an increased risk of developing ovarian cancer when compared to subfertile women who don’t undergo ART, according to a new study.

The results suggest that nulliparity is likely responsible for the increased risk of ovarian cancer observed in patients treated with ART, the researchers said.

Earlier, shorter studies had only compared ART-treated women with women from the general population.

“Subfertile women differ from women in the general population according to several ovarian cancer risk factors. Therefore, to estimate the risk of ovarian cancer associated with ART, it was important to include a comparison group of women who were subfertile and not treated with ART,” said senior study author Flora E. van Leeuwen, PhD, of Netherlands Cancer Institute in Amsterdam.

She and her colleagues conducted a nationwide cohort study of 30,625 women who received ovarian stimulation for ART during 1983-2000 and 9,988 women who received fertility treatments other than ART.

Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group.

The researchers reported the results in the Journal of the National Cancer Institute.
 

Risk of ovarian cancer

Women treated with ART were no more likely to develop ovarian cancer than subfertile women not treated with ART (adjusted hazard ratio, 1.02), but the ART group did have an increased risk of ovarian cancer when compared to the general population (standardized incidence ratio, 1.43).

“This, however, turned out to be due to the fact that the women who had received ART were less likely to have children. Not having children is a known risk factor for ovarian cancer,” Dr. van Leeuwen said.

Women with more ART procedures that resulted in the birth of a child were at lower risk of developing ovarian cancer, compared with women without any successful cycle (Ptrend = .001). However, women who had only cycles not resulting in a birth were not at higher risk of ovarian cancer when they had a greater number of cycles.

“These results indicate that parity decreases the risk of ovarian cancer, also in ART-treated women. But more unsuccessful ART cycles do not increase the risk of ovarian cancer,” Dr. van Leeuwen said.
 

Risk of borderline ovarian tumors

The risk of developing borderline ovarian tumors was roughly twice as high in women who had received ART, both compared with women who had received other fertility treatments (hazard ratio, 1.84) and women from the general population (standardized incidence ratio, 2.20).

However, the risk of developing borderline ovarian tumors did not increase in women who had received multiple ART procedures.

“If there was a causal association between ART and increased risk of borderline ovarian tumors, we would expect to see this risk increase with a greater number of ART procedures from more hormones and more stimulation of the ovaries. This makes the direct link between ART and increased risk of borderline tumors a bit uncertain. It might be caused by other factors, such as the severity of infertility,” Dr. van Leeuwen said.

Borderline ovarian tumors are rare in the general population in the Netherlands, and women who develop these tumors generally have a good prognosis, she said.

The risk of developing a borderline tumor before the age of 55 for women in the Netherlands is approximately 0.2%. After ART, the study found a risk of approximately 0.3%.

Causal associations with ART 'unlikely'

“Women who develop cancer and have undergone ART procedures in the past may wonder whether their cancer may be caused by ART. Based on the results from our study, that seems unlikely, and that is a very reassuring message from practicing oncologists to women diagnosed with ovarian cancer. Another important message is that, in ART-treated women, increasing parity reduces the risk of ovarian cancer,” Dr. van Leeuwen said.

She added that the risk of borderline ovarian tumors did not increase in women who received multiple ART procedures, “which makes it somewhat less likely that ART would have caused their borderline ovarian tumor.”

The study does not exclude the possibility that ART might increase the risk of ovarian tumors after age 60.

“Despite our long follow-up, the age of the women at the end of our study was still relatively young [average 56 years]. Because the incidence of ovarian cancer increases with older age, it is vital to continue to follow these women. Only then can we be sure that ART does not increase the risk of ovarian tumors in the very long run,” Dr. van Leeuwen said.

“This study offers confirmation of several previous studies and provides reassurance about the risk of ovarian cancer after ART procedures,” said Daniel Kenigsberg, MD, of RMA Long Island IVF in New York. Dr. Kenigsberg was not involved in this study but has performed more than 30,000 ART procedures over the past 32 years.

“Researchers have looked at whether fertility drugs cause ovarian cancer in different ways and in different countries, and there is no cause-and-effect relationship. There was no dose-response relationship between ART and ovarian tumors in this study. It’s more likely there is something wrong with the women’s ovaries that lead to borderline tumors and infertility more than any treatment,” Dr. Kenigsberg added.

“Perhaps both fertility and cancer relate to an underlying ovarian issue, but this would not explain the increased cancer incidence in those who never attempted pregnancy, that is, women who are voluntarily childless. Pregnancy is statistically protective: more pregnancies lead to less ovarian cancer, but this is far from absolute,” he explained.

Dr. Kenigsberg suggested that oncologists should be aware of a patient’s obstetrical history and fertility history as well as any related medical interventions.

“Borderline tumors look like cancer and have histologic features of cancer but do not meet the criteria for a cancer diagnosis,” he said. “They require close surveillance because their relationship to the development of full-fledged cancer is uncertain.”

This research was supported by grants from the Dutch Cancer Society. The authors and Dr. Kenigsberg have no conflicts of interest.

Women who receive ovarian stimulation for assisted reproductive technology (ART) procedures don’t have an increased risk of developing ovarian cancer when compared to subfertile women who don’t undergo ART, according to a new study.

The results suggest that nulliparity is likely responsible for the increased risk of ovarian cancer observed in patients treated with ART, the researchers said.

Earlier, shorter studies had only compared ART-treated women with women from the general population.

“Subfertile women differ from women in the general population according to several ovarian cancer risk factors. Therefore, to estimate the risk of ovarian cancer associated with ART, it was important to include a comparison group of women who were subfertile and not treated with ART,” said senior study author Flora E. van Leeuwen, PhD, of Netherlands Cancer Institute in Amsterdam.

She and her colleagues conducted a nationwide cohort study of 30,625 women who received ovarian stimulation for ART during 1983-2000 and 9,988 women who received fertility treatments other than ART.

Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group.

The researchers reported the results in the Journal of the National Cancer Institute.
 

Risk of ovarian cancer

Women treated with ART were no more likely to develop ovarian cancer than subfertile women not treated with ART (adjusted hazard ratio, 1.02), but the ART group did have an increased risk of ovarian cancer when compared to the general population (standardized incidence ratio, 1.43).

“This, however, turned out to be due to the fact that the women who had received ART were less likely to have children. Not having children is a known risk factor for ovarian cancer,” Dr. van Leeuwen said.

Women with more ART procedures that resulted in the birth of a child were at lower risk of developing ovarian cancer, compared with women without any successful cycle (Ptrend = .001). However, women who had only cycles not resulting in a birth were not at higher risk of ovarian cancer when they had a greater number of cycles.

“These results indicate that parity decreases the risk of ovarian cancer, also in ART-treated women. But more unsuccessful ART cycles do not increase the risk of ovarian cancer,” Dr. van Leeuwen said.
 

Risk of borderline ovarian tumors

The risk of developing borderline ovarian tumors was roughly twice as high in women who had received ART, both compared with women who had received other fertility treatments (hazard ratio, 1.84) and women from the general population (standardized incidence ratio, 2.20).

However, the risk of developing borderline ovarian tumors did not increase in women who had received multiple ART procedures.

“If there was a causal association between ART and increased risk of borderline ovarian tumors, we would expect to see this risk increase with a greater number of ART procedures from more hormones and more stimulation of the ovaries. This makes the direct link between ART and increased risk of borderline tumors a bit uncertain. It might be caused by other factors, such as the severity of infertility,” Dr. van Leeuwen said.

Borderline ovarian tumors are rare in the general population in the Netherlands, and women who develop these tumors generally have a good prognosis, she said.

The risk of developing a borderline tumor before the age of 55 for women in the Netherlands is approximately 0.2%. After ART, the study found a risk of approximately 0.3%.

Causal associations with ART 'unlikely'

“Women who develop cancer and have undergone ART procedures in the past may wonder whether their cancer may be caused by ART. Based on the results from our study, that seems unlikely, and that is a very reassuring message from practicing oncologists to women diagnosed with ovarian cancer. Another important message is that, in ART-treated women, increasing parity reduces the risk of ovarian cancer,” Dr. van Leeuwen said.

She added that the risk of borderline ovarian tumors did not increase in women who received multiple ART procedures, “which makes it somewhat less likely that ART would have caused their borderline ovarian tumor.”

The study does not exclude the possibility that ART might increase the risk of ovarian tumors after age 60.

“Despite our long follow-up, the age of the women at the end of our study was still relatively young [average 56 years]. Because the incidence of ovarian cancer increases with older age, it is vital to continue to follow these women. Only then can we be sure that ART does not increase the risk of ovarian tumors in the very long run,” Dr. van Leeuwen said.

“This study offers confirmation of several previous studies and provides reassurance about the risk of ovarian cancer after ART procedures,” said Daniel Kenigsberg, MD, of RMA Long Island IVF in New York. Dr. Kenigsberg was not involved in this study but has performed more than 30,000 ART procedures over the past 32 years.

“Researchers have looked at whether fertility drugs cause ovarian cancer in different ways and in different countries, and there is no cause-and-effect relationship. There was no dose-response relationship between ART and ovarian tumors in this study. It’s more likely there is something wrong with the women’s ovaries that lead to borderline tumors and infertility more than any treatment,” Dr. Kenigsberg added.

“Perhaps both fertility and cancer relate to an underlying ovarian issue, but this would not explain the increased cancer incidence in those who never attempted pregnancy, that is, women who are voluntarily childless. Pregnancy is statistically protective: more pregnancies lead to less ovarian cancer, but this is far from absolute,” he explained.

Dr. Kenigsberg suggested that oncologists should be aware of a patient’s obstetrical history and fertility history as well as any related medical interventions.

“Borderline tumors look like cancer and have histologic features of cancer but do not meet the criteria for a cancer diagnosis,” he said. “They require close surveillance because their relationship to the development of full-fledged cancer is uncertain.”

This research was supported by grants from the Dutch Cancer Society. The authors and Dr. Kenigsberg have no conflicts of interest.

Dexamethasone can have a detrimental effect on survival in patients with glioblastoma who are receiving immunotherapy, according to a study published in Clinical Cancer Research.

Investigators found that baseline dexamethasone use was associated with poor overall survival (OS) in glioblastoma patients receiving anti–PD-1 or anti–PD-L1 therapy. In fact, in a multivariable analysis, baseline dexamethasone use was the strongest predictor of poor survival.

These results “support accumulating concerns that corticosteroids can be detrimental to immunotherapy for oncology patients,” wrote senior study author David Reardon, MD, of Dana-Farber Cancer Institute in Boston and colleagues.

The concerns are particularly relevant for glioblastoma patients because dexamethasone is a cornerstone of glioblastoma therapy, being used to reduce tumor-associated edema. Patients often receive dexamethasone early on and in significant doses for a protracted period of time to stay ahead of evolving symptoms.

However, the current study suggests dexamethasone and other corticosteroids may be contraindicated in glioblastoma patients on immunotherapy. Therefore, Dr. Reardon and colleagues recommended “careful evaluation of dexamethasone use” in these patients.

“If a glioblastoma patient requires corticosteroids, and they often do for debilitating symptoms, only use these drugs if the patient really needs them,” Dr. Reardon advised. “Start at a low dose and use the shortest treatment interval possible.”
 

Preclinical and clinical results

Dr. Reardon and colleagues initially evaluated the effects of dexamethasone when administered with PD-1 blockade and/or radiotherapy in an immunocompetent syngeneic mouse model.

Most mice that received anti–PD-1 monotherapy were cured, but the benefit of anti–PD-1 therapy was significantly diminished, in a dose-dependent manner, when dexamethasone was added.

At 100 days, the OS rate was about 76% in the anti–PD-1 monotherapy group, 47% when dexamethasone was given at 1 mg/kg, 31% with dexamethasone at 2.5 mg/kg, and 27% with dexamethasone at 10 mg/kg.

A mechanistic study, including analysis of immune cells in the spleen, showed that dexamethasone decreased intratumoral T cells and systemic levels of T cells, natural killer cells, and myeloid cells, while qualitatively impairing lymphocyte function. The mechanism of T-cell depletion included induction of apoptosis, which was noted as soon as 1 hour after the dexamethasone dose, Dr. Reardon said.

The researchers also evaluated 181 consecutive glioblastoma patients treated with PD-1– or PD-L1–targeted therapy. The study included a multivariable statistical analysis that accounted for age, performance status, extent of resection, size of tumor, bulk tumor burden, and MGMT promoter methylation status.

In an initial unadjusted analysis, baseline dexamethasone decreased the median OS to 8.1 months when it was given at less than 2 mg daily and 6.3 months when given at 2 mg or more daily. The median OS was 13.1 months for patients who did not receive dexamethasone.

After multivariable adjustment, baseline dexamethasone eliminated the survival benefit of immunotherapy, the researchers said. The hazard ratio was 2.16 (P = .003) when dexamethasone was given at less than 2 mg daily and 1.97 (P = .005) with dexamethasone at 2 mg or more daily, compared with no baseline dexamethasone.

In fact, the strongest negative risk factor for OS was the use of dexamethasone at initiation of checkpoint inhibitor therapy.
 

Implications: Use corticosteroids ‘very judiciously’

The results of this research suggest “corticosteroids can be detrimental when used along with checkpoint inhibitors,” Dr. Reardon said. He added that this effect could extend to other immunotherapies, such as vaccines, cellular therapies, and oncolytic viruses.

“We need to understand what is driving the inflammatory response,” Dr. Reardon said. “Other targets in the downstream pathway may be regulated to avoid the detrimental effect of corticosteroids.”

Ongoing prospective clinical trials need to build in whether concurrent use of corticosteroids leads to poorer outcomes, according to Dr. Reardon.

“We are validating this prospectively in ongoing clinical trials to evaluate differences in outcome in glioblastoma patients and exploring different types of immunotherapies,” he said.

Though questions remain, Dr. Reardon advises judicious use of corticosteroids or even substituting corticosteroids with bevacizumab in glioblastoma patients.

“If a glioblastoma patient develops debilitating symptoms due to swelling in the brain and is a candidate for immunotherapy, then consider using bevacizumab to avoid using corticosteroids,” Dr. Reardon said, adding that this is being tested prospectively in a clinical trial as well.

“We know corticosteroids have a host of side effects. An additional side effect may be limiting immune function in brain cancer patients and jeopardizing the potential benefits of immunotherapy going forward. I implore practicing oncologists to use corticosteroids very judiciously and as little as possible for as little time as possible,” Dr. Reardon said.

This research was funded by grants from the National Institutes of Health and support from various foundations and institutions. The researchers disclosed relationships with many pharmaceutical companies.

SOURCE: Iorgulescu JB et al. Clin Cancer Res. 2020 Nov 25. doi: 10.1158/1078-0432.CCR-20-2291.

Dexamethasone can have a detrimental effect on survival in patients with glioblastoma who are receiving immunotherapy, according to a study published in Clinical Cancer Research.

Investigators found that baseline dexamethasone use was associated with poor overall survival (OS) in glioblastoma patients receiving anti–PD-1 or anti–PD-L1 therapy. In fact, in a multivariable analysis, baseline dexamethasone use was the strongest predictor of poor survival.

These results “support accumulating concerns that corticosteroids can be detrimental to immunotherapy for oncology patients,” wrote senior study author David Reardon, MD, of Dana-Farber Cancer Institute in Boston and colleagues.

The concerns are particularly relevant for glioblastoma patients because dexamethasone is a cornerstone of glioblastoma therapy, being used to reduce tumor-associated edema. Patients often receive dexamethasone early on and in significant doses for a protracted period of time to stay ahead of evolving symptoms.

However, the current study suggests dexamethasone and other corticosteroids may be contraindicated in glioblastoma patients on immunotherapy. Therefore, Dr. Reardon and colleagues recommended “careful evaluation of dexamethasone use” in these patients.

“If a glioblastoma patient requires corticosteroids, and they often do for debilitating symptoms, only use these drugs if the patient really needs them,” Dr. Reardon advised. “Start at a low dose and use the shortest treatment interval possible.”
 

Preclinical and clinical results

Dr. Reardon and colleagues initially evaluated the effects of dexamethasone when administered with PD-1 blockade and/or radiotherapy in an immunocompetent syngeneic mouse model.

Most mice that received anti–PD-1 monotherapy were cured, but the benefit of anti–PD-1 therapy was significantly diminished, in a dose-dependent manner, when dexamethasone was added.

At 100 days, the OS rate was about 76% in the anti–PD-1 monotherapy group, 47% when dexamethasone was given at 1 mg/kg, 31% with dexamethasone at 2.5 mg/kg, and 27% with dexamethasone at 10 mg/kg.

A mechanistic study, including analysis of immune cells in the spleen, showed that dexamethasone decreased intratumoral T cells and systemic levels of T cells, natural killer cells, and myeloid cells, while qualitatively impairing lymphocyte function. The mechanism of T-cell depletion included induction of apoptosis, which was noted as soon as 1 hour after the dexamethasone dose, Dr. Reardon said.

The researchers also evaluated 181 consecutive glioblastoma patients treated with PD-1– or PD-L1–targeted therapy. The study included a multivariable statistical analysis that accounted for age, performance status, extent of resection, size of tumor, bulk tumor burden, and MGMT promoter methylation status.

In an initial unadjusted analysis, baseline dexamethasone decreased the median OS to 8.1 months when it was given at less than 2 mg daily and 6.3 months when given at 2 mg or more daily. The median OS was 13.1 months for patients who did not receive dexamethasone.

After multivariable adjustment, baseline dexamethasone eliminated the survival benefit of immunotherapy, the researchers said. The hazard ratio was 2.16 (P = .003) when dexamethasone was given at less than 2 mg daily and 1.97 (P = .005) with dexamethasone at 2 mg or more daily, compared with no baseline dexamethasone.

In fact, the strongest negative risk factor for OS was the use of dexamethasone at initiation of checkpoint inhibitor therapy.
 

Implications: Use corticosteroids ‘very judiciously’

The results of this research suggest “corticosteroids can be detrimental when used along with checkpoint inhibitors,” Dr. Reardon said. He added that this effect could extend to other immunotherapies, such as vaccines, cellular therapies, and oncolytic viruses.

“We need to understand what is driving the inflammatory response,” Dr. Reardon said. “Other targets in the downstream pathway may be regulated to avoid the detrimental effect of corticosteroids.”

Ongoing prospective clinical trials need to build in whether concurrent use of corticosteroids leads to poorer outcomes, according to Dr. Reardon.

“We are validating this prospectively in ongoing clinical trials to evaluate differences in outcome in glioblastoma patients and exploring different types of immunotherapies,” he said.

Though questions remain, Dr. Reardon advises judicious use of corticosteroids or even substituting corticosteroids with bevacizumab in glioblastoma patients.

“If a glioblastoma patient develops debilitating symptoms due to swelling in the brain and is a candidate for immunotherapy, then consider using bevacizumab to avoid using corticosteroids,” Dr. Reardon said, adding that this is being tested prospectively in a clinical trial as well.

“We know corticosteroids have a host of side effects. An additional side effect may be limiting immune function in brain cancer patients and jeopardizing the potential benefits of immunotherapy going forward. I implore practicing oncologists to use corticosteroids very judiciously and as little as possible for as little time as possible,” Dr. Reardon said.

This research was funded by grants from the National Institutes of Health and support from various foundations and institutions. The researchers disclosed relationships with many pharmaceutical companies.

SOURCE: Iorgulescu JB et al. Clin Cancer Res. 2020 Nov 25. doi: 10.1158/1078-0432.CCR-20-2291.

Dexamethasone can have a detrimental effect on survival in patients with glioblastoma who are receiving immunotherapy, according to a study published in Clinical Cancer Research.

Investigators found that baseline dexamethasone use was associated with poor overall survival (OS) in glioblastoma patients receiving anti–PD-1 or anti–PD-L1 therapy. In fact, in a multivariable analysis, baseline dexamethasone use was the strongest predictor of poor survival.

These results “support accumulating concerns that corticosteroids can be detrimental to immunotherapy for oncology patients,” wrote senior study author David Reardon, MD, of Dana-Farber Cancer Institute in Boston and colleagues.

The concerns are particularly relevant for glioblastoma patients because dexamethasone is a cornerstone of glioblastoma therapy, being used to reduce tumor-associated edema. Patients often receive dexamethasone early on and in significant doses for a protracted period of time to stay ahead of evolving symptoms.

However, the current study suggests dexamethasone and other corticosteroids may be contraindicated in glioblastoma patients on immunotherapy. Therefore, Dr. Reardon and colleagues recommended “careful evaluation of dexamethasone use” in these patients.

“If a glioblastoma patient requires corticosteroids, and they often do for debilitating symptoms, only use these drugs if the patient really needs them,” Dr. Reardon advised. “Start at a low dose and use the shortest treatment interval possible.”
 

Preclinical and clinical results

Dr. Reardon and colleagues initially evaluated the effects of dexamethasone when administered with PD-1 blockade and/or radiotherapy in an immunocompetent syngeneic mouse model.

Most mice that received anti–PD-1 monotherapy were cured, but the benefit of anti–PD-1 therapy was significantly diminished, in a dose-dependent manner, when dexamethasone was added.

At 100 days, the OS rate was about 76% in the anti–PD-1 monotherapy group, 47% when dexamethasone was given at 1 mg/kg, 31% with dexamethasone at 2.5 mg/kg, and 27% with dexamethasone at 10 mg/kg.

A mechanistic study, including analysis of immune cells in the spleen, showed that dexamethasone decreased intratumoral T cells and systemic levels of T cells, natural killer cells, and myeloid cells, while qualitatively impairing lymphocyte function. The mechanism of T-cell depletion included induction of apoptosis, which was noted as soon as 1 hour after the dexamethasone dose, Dr. Reardon said.

The researchers also evaluated 181 consecutive glioblastoma patients treated with PD-1– or PD-L1–targeted therapy. The study included a multivariable statistical analysis that accounted for age, performance status, extent of resection, size of tumor, bulk tumor burden, and MGMT promoter methylation status.

In an initial unadjusted analysis, baseline dexamethasone decreased the median OS to 8.1 months when it was given at less than 2 mg daily and 6.3 months when given at 2 mg or more daily. The median OS was 13.1 months for patients who did not receive dexamethasone.

After multivariable adjustment, baseline dexamethasone eliminated the survival benefit of immunotherapy, the researchers said. The hazard ratio was 2.16 (P = .003) when dexamethasone was given at less than 2 mg daily and 1.97 (P = .005) with dexamethasone at 2 mg or more daily, compared with no baseline dexamethasone.

In fact, the strongest negative risk factor for OS was the use of dexamethasone at initiation of checkpoint inhibitor therapy.
 

Implications: Use corticosteroids ‘very judiciously’

The results of this research suggest “corticosteroids can be detrimental when used along with checkpoint inhibitors,” Dr. Reardon said. He added that this effect could extend to other immunotherapies, such as vaccines, cellular therapies, and oncolytic viruses.

“We need to understand what is driving the inflammatory response,” Dr. Reardon said. “Other targets in the downstream pathway may be regulated to avoid the detrimental effect of corticosteroids.”

Ongoing prospective clinical trials need to build in whether concurrent use of corticosteroids leads to poorer outcomes, according to Dr. Reardon.

“We are validating this prospectively in ongoing clinical trials to evaluate differences in outcome in glioblastoma patients and exploring different types of immunotherapies,” he said.

Though questions remain, Dr. Reardon advises judicious use of corticosteroids or even substituting corticosteroids with bevacizumab in glioblastoma patients.

“If a glioblastoma patient develops debilitating symptoms due to swelling in the brain and is a candidate for immunotherapy, then consider using bevacizumab to avoid using corticosteroids,” Dr. Reardon said, adding that this is being tested prospectively in a clinical trial as well.

“We know corticosteroids have a host of side effects. An additional side effect may be limiting immune function in brain cancer patients and jeopardizing the potential benefits of immunotherapy going forward. I implore practicing oncologists to use corticosteroids very judiciously and as little as possible for as little time as possible,” Dr. Reardon said.

This research was funded by grants from the National Institutes of Health and support from various foundations and institutions. The researchers disclosed relationships with many pharmaceutical companies.

SOURCE: Iorgulescu JB et al. Clin Cancer Res. 2020 Nov 25. doi: 10.1158/1078-0432.CCR-20-2291.

Many survivors of localized renal cell carcinoma (RCC) experience fear of cancer recurrence (FCR), according to a survey.

About 55% of survivors surveyed expressed this fear, which is higher than the average prevalence among patients diagnosed with other cancers.

Younger and female RCC survivors appear to be at particular risk, but disease stage and time since diagnosis are not associated with FCR, according to the survey.

The results were published in JCO Oncology Practice.

The majority of existing studies concerning FCR have been of survivors of breast, prostate, and gynecologic cancers. For the first time, researchers examined this issue in RCC survivors in a large trial.

More than 1,000 survivors of localized RCC were asked to participate in a survey through social media by the Kidney Cancer Research Alliance.

A total of 412 survivors were included in the analysis. They had a median age of 54 years (range, 30-80 years), were mostly female (79.4%), were mostly well educated (58.3%), and had a median of 17.5 months’ time since diagnosis.

More than half of patients were diagnosed with stage I disease, and about two-thirds had a clear understanding of their diagnosis.
 

Results: FCR persists in RCC

Two-thirds of the survivors had a high prevalence of moderate to severe distress, and 54.9% reported FCR.

“This is the first study to assess fear of cancer recurrence in RCC,” said lead study author Cristiane Decat Bergerot, PhD, who conducted the research during a fellowship at City of Hope in Duarte, Calif. She is now director of the department of psycho-oncology at CETTRO Cancer Research Hospital in Brasilia, Brazil.

“RCC patients really experience this emotion,” Dr. Bergerot said. “Other emotional symptoms, even stress, tend to lower over time. This does not happen with FCR in RCC patients. More than 3 years later, they still had the same prevalence of FCR.”

The prevalence of FCR was not associated with race, education level, country, residential area, cancer care facility type, travel time to hospital, or clinical characteristics such as disease stage and time since diagnosis.

However, higher FCR was associated with female gender, younger age, and lack of understanding of diagnosis. For younger and female patients, the social and emotional consequences of RCC may make it hard for them to keep up with daily activities. Younger patients may have multiple social roles and responsibilities, and an RCC diagnosis interrupts their life.

Even though RCC is more prevalent in males, “females traditionally have no fear of saying they are not doing well with diagnosis or treatment. Women appear to be more open to support,” Dr. Bergerot said.
 

Interventions and support

Psychosocial support with targeted interventions can help address FCR for RCC patients, according to Dr. Bergerot. For example, researchers are developing an app to allow for psychosocial intervention at home to help patients cope with FCR, she said, noting that clinicians in cancer centers more often see metastatic disease, not localized disease.

“Clinicians can teach patients to be more comfortable and feel less anxious about their prognosis and also help them participate in treatment decision-making,” Dr. Bergerot said. “When a RCC patient worries too much about cancer recurrence, refer the patient to a psychosocial team. The patient can receive practical advice to balance emotional symptoms, learn more about their current situation, and find more information through cancer support groups.”

“FCR is a key factor underlying emotional and behavioral difficulties faced by survivors of cancer,” said Daniel L. Hall, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in this study. “Clinicians treating cancer survivors are well positioned to assess and intervene on FCR, distress, and health behaviors.”  

Dr. Hall noted that these fears are a near-ubiquitous concern for cancer survivors.

“Inherently, managing FCR requires acknowledging and facing the uncertainty about one’s future health, which, of course, for all of us is unpredictable, ambiguous, and ever-changing. Although many patients who fear recurrence are fortunate to have a low objective risk of recurrence, I believe patients facing cancer, regardless of demographic or medical characteristics, can feel afraid when facing an unknown, possibly dangerous future,” Dr. Hall said. 

Calls for interventions targeting FCR have emphasized the need for evidence-based treatments and multimodal interventions that teach a variety of targeted skills. Cognitive behavioral therapy (CBT) and mind-body interventions are being studied to address FCR.

“Our team conducted a meta-analysis of randomized clinical trials of these interventions and found that pooled effects were significant, yet small, suggesting the need for further intervention development,” Dr. Hall said. “Through funding from the NIH’s National Center for Complementary and Integrative Health, we are currently evaluating a multimodal, group-based intervention that integrates many of the most effective FCR management skills: CBT, mindfulness meditation, relaxation response training, and positive psychology.”

Harvard researchers recently published encouraging results from a small pilot study of a group intervention. The next step is to test a remote, synchronous program in a randomized trial, with recruitment anticipated in early 2021.

“In addition to our work, other groups are developing asynchronous interventions that cancer survivors can use by accessing a website, which may appeal to survivors looking for information quickly or who may not be interested in participating in a group intervention,” Dr. Hall said.

The current study did not receive specific funding. The authors disclosed relationships with many companies, which can be found in the paper. Dr. Hall has no disclosures.

SOURCE: Bergerot CD et al. JCO Oncol Pract. 2020 Nov;16(11):e1264-71.

Many survivors of localized renal cell carcinoma (RCC) experience fear of cancer recurrence (FCR), according to a survey.

About 55% of survivors surveyed expressed this fear, which is higher than the average prevalence among patients diagnosed with other cancers.

Younger and female RCC survivors appear to be at particular risk, but disease stage and time since diagnosis are not associated with FCR, according to the survey.

The results were published in JCO Oncology Practice.

The majority of existing studies concerning FCR have been of survivors of breast, prostate, and gynecologic cancers. For the first time, researchers examined this issue in RCC survivors in a large trial.

More than 1,000 survivors of localized RCC were asked to participate in a survey through social media by the Kidney Cancer Research Alliance.

A total of 412 survivors were included in the analysis. They had a median age of 54 years (range, 30-80 years), were mostly female (79.4%), were mostly well educated (58.3%), and had a median of 17.5 months’ time since diagnosis.

More than half of patients were diagnosed with stage I disease, and about two-thirds had a clear understanding of their diagnosis.
 

Results: FCR persists in RCC

Two-thirds of the survivors had a high prevalence of moderate to severe distress, and 54.9% reported FCR.

“This is the first study to assess fear of cancer recurrence in RCC,” said lead study author Cristiane Decat Bergerot, PhD, who conducted the research during a fellowship at City of Hope in Duarte, Calif. She is now director of the department of psycho-oncology at CETTRO Cancer Research Hospital in Brasilia, Brazil.

“RCC patients really experience this emotion,” Dr. Bergerot said. “Other emotional symptoms, even stress, tend to lower over time. This does not happen with FCR in RCC patients. More than 3 years later, they still had the same prevalence of FCR.”

The prevalence of FCR was not associated with race, education level, country, residential area, cancer care facility type, travel time to hospital, or clinical characteristics such as disease stage and time since diagnosis.

However, higher FCR was associated with female gender, younger age, and lack of understanding of diagnosis. For younger and female patients, the social and emotional consequences of RCC may make it hard for them to keep up with daily activities. Younger patients may have multiple social roles and responsibilities, and an RCC diagnosis interrupts their life.

Even though RCC is more prevalent in males, “females traditionally have no fear of saying they are not doing well with diagnosis or treatment. Women appear to be more open to support,” Dr. Bergerot said.
 

Interventions and support

Psychosocial support with targeted interventions can help address FCR for RCC patients, according to Dr. Bergerot. For example, researchers are developing an app to allow for psychosocial intervention at home to help patients cope with FCR, she said, noting that clinicians in cancer centers more often see metastatic disease, not localized disease.

“Clinicians can teach patients to be more comfortable and feel less anxious about their prognosis and also help them participate in treatment decision-making,” Dr. Bergerot said. “When a RCC patient worries too much about cancer recurrence, refer the patient to a psychosocial team. The patient can receive practical advice to balance emotional symptoms, learn more about their current situation, and find more information through cancer support groups.”

“FCR is a key factor underlying emotional and behavioral difficulties faced by survivors of cancer,” said Daniel L. Hall, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in this study. “Clinicians treating cancer survivors are well positioned to assess and intervene on FCR, distress, and health behaviors.”  

Dr. Hall noted that these fears are a near-ubiquitous concern for cancer survivors.

“Inherently, managing FCR requires acknowledging and facing the uncertainty about one’s future health, which, of course, for all of us is unpredictable, ambiguous, and ever-changing. Although many patients who fear recurrence are fortunate to have a low objective risk of recurrence, I believe patients facing cancer, regardless of demographic or medical characteristics, can feel afraid when facing an unknown, possibly dangerous future,” Dr. Hall said. 

Calls for interventions targeting FCR have emphasized the need for evidence-based treatments and multimodal interventions that teach a variety of targeted skills. Cognitive behavioral therapy (CBT) and mind-body interventions are being studied to address FCR.

“Our team conducted a meta-analysis of randomized clinical trials of these interventions and found that pooled effects were significant, yet small, suggesting the need for further intervention development,” Dr. Hall said. “Through funding from the NIH’s National Center for Complementary and Integrative Health, we are currently evaluating a multimodal, group-based intervention that integrates many of the most effective FCR management skills: CBT, mindfulness meditation, relaxation response training, and positive psychology.”

Harvard researchers recently published encouraging results from a small pilot study of a group intervention. The next step is to test a remote, synchronous program in a randomized trial, with recruitment anticipated in early 2021.

“In addition to our work, other groups are developing asynchronous interventions that cancer survivors can use by accessing a website, which may appeal to survivors looking for information quickly or who may not be interested in participating in a group intervention,” Dr. Hall said.

The current study did not receive specific funding. The authors disclosed relationships with many companies, which can be found in the paper. Dr. Hall has no disclosures.

SOURCE: Bergerot CD et al. JCO Oncol Pract. 2020 Nov;16(11):e1264-71.

Many survivors of localized renal cell carcinoma (RCC) experience fear of cancer recurrence (FCR), according to a survey.

About 55% of survivors surveyed expressed this fear, which is higher than the average prevalence among patients diagnosed with other cancers.

Younger and female RCC survivors appear to be at particular risk, but disease stage and time since diagnosis are not associated with FCR, according to the survey.

The results were published in JCO Oncology Practice.

The majority of existing studies concerning FCR have been of survivors of breast, prostate, and gynecologic cancers. For the first time, researchers examined this issue in RCC survivors in a large trial.

More than 1,000 survivors of localized RCC were asked to participate in a survey through social media by the Kidney Cancer Research Alliance.

A total of 412 survivors were included in the analysis. They had a median age of 54 years (range, 30-80 years), were mostly female (79.4%), were mostly well educated (58.3%), and had a median of 17.5 months’ time since diagnosis.

More than half of patients were diagnosed with stage I disease, and about two-thirds had a clear understanding of their diagnosis.
 

Results: FCR persists in RCC

Two-thirds of the survivors had a high prevalence of moderate to severe distress, and 54.9% reported FCR.

“This is the first study to assess fear of cancer recurrence in RCC,” said lead study author Cristiane Decat Bergerot, PhD, who conducted the research during a fellowship at City of Hope in Duarte, Calif. She is now director of the department of psycho-oncology at CETTRO Cancer Research Hospital in Brasilia, Brazil.

“RCC patients really experience this emotion,” Dr. Bergerot said. “Other emotional symptoms, even stress, tend to lower over time. This does not happen with FCR in RCC patients. More than 3 years later, they still had the same prevalence of FCR.”

The prevalence of FCR was not associated with race, education level, country, residential area, cancer care facility type, travel time to hospital, or clinical characteristics such as disease stage and time since diagnosis.

However, higher FCR was associated with female gender, younger age, and lack of understanding of diagnosis. For younger and female patients, the social and emotional consequences of RCC may make it hard for them to keep up with daily activities. Younger patients may have multiple social roles and responsibilities, and an RCC diagnosis interrupts their life.

Even though RCC is more prevalent in males, “females traditionally have no fear of saying they are not doing well with diagnosis or treatment. Women appear to be more open to support,” Dr. Bergerot said.
 

Interventions and support

Psychosocial support with targeted interventions can help address FCR for RCC patients, according to Dr. Bergerot. For example, researchers are developing an app to allow for psychosocial intervention at home to help patients cope with FCR, she said, noting that clinicians in cancer centers more often see metastatic disease, not localized disease.

“Clinicians can teach patients to be more comfortable and feel less anxious about their prognosis and also help them participate in treatment decision-making,” Dr. Bergerot said. “When a RCC patient worries too much about cancer recurrence, refer the patient to a psychosocial team. The patient can receive practical advice to balance emotional symptoms, learn more about their current situation, and find more information through cancer support groups.”

“FCR is a key factor underlying emotional and behavioral difficulties faced by survivors of cancer,” said Daniel L. Hall, PhD, of Massachusetts General Hospital and Harvard Medical School in Boston, who was not involved in this study. “Clinicians treating cancer survivors are well positioned to assess and intervene on FCR, distress, and health behaviors.”  

Dr. Hall noted that these fears are a near-ubiquitous concern for cancer survivors.

“Inherently, managing FCR requires acknowledging and facing the uncertainty about one’s future health, which, of course, for all of us is unpredictable, ambiguous, and ever-changing. Although many patients who fear recurrence are fortunate to have a low objective risk of recurrence, I believe patients facing cancer, regardless of demographic or medical characteristics, can feel afraid when facing an unknown, possibly dangerous future,” Dr. Hall said. 

Calls for interventions targeting FCR have emphasized the need for evidence-based treatments and multimodal interventions that teach a variety of targeted skills. Cognitive behavioral therapy (CBT) and mind-body interventions are being studied to address FCR.

“Our team conducted a meta-analysis of randomized clinical trials of these interventions and found that pooled effects were significant, yet small, suggesting the need for further intervention development,” Dr. Hall said. “Through funding from the NIH’s National Center for Complementary and Integrative Health, we are currently evaluating a multimodal, group-based intervention that integrates many of the most effective FCR management skills: CBT, mindfulness meditation, relaxation response training, and positive psychology.”

Harvard researchers recently published encouraging results from a small pilot study of a group intervention. The next step is to test a remote, synchronous program in a randomized trial, with recruitment anticipated in early 2021.

“In addition to our work, other groups are developing asynchronous interventions that cancer survivors can use by accessing a website, which may appeal to survivors looking for information quickly or who may not be interested in participating in a group intervention,” Dr. Hall said.

The current study did not receive specific funding. The authors disclosed relationships with many companies, which can be found in the paper. Dr. Hall has no disclosures.

SOURCE: Bergerot CD et al. JCO Oncol Pract. 2020 Nov;16(11):e1264-71.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Black patients with extensive-stage small cell lung cancer (ES-SCLC) are less likely to receive chemotherapy but have better survival, compared with White patients, according to a study published in JTO Clinical Research and Reports.

This study provides a large-scale analysis of real-world data identifying racial and socioeconomic factors impacting systemic therapy delivery and survival in ES-SCLC.

“The most important finding was the significant disparity in receipt of chemotherapy,” said study author Umit Tapan, MD, of Boston Medical Center.

“Black individuals with ES-SCLC were less likely to receive chemotherapy compared to Whites and other racial groups. Similarly, elderly, uninsured patients, patients with nonprivate health insurance, and those with lower education levels were less likely to be treated with chemotherapy,” Dr. Tapan said.

Using the National Cancer Data Base (NCDB), Dr. Tapan and colleagues identified 148,961 patients who were diagnosed with stage IV ES-SCLC during 2004-2016. In all, 82,592 patients were included in the study.
 

Results: Treatment and survival

Compared with White patients, Black patients (adjusted odds ratio, 0.85; P = .0004) and patients from other racial groups (aOR, 0.87; P = .126) had lower odds of receiving chemotherapy on multivariate analysis.

However, survival was superior in Black patients (adjusted hazard ratio, 0.92; P < .0001) and other non-White patients (aHR 0.86; P < .0001).

“We speculate that additional factors, such as performance status, which is not captured by NCDB, might have accounted for better survival for Black patients,” Dr. Tapan said, noting that the analysis was adjusted for known possible confounding factors, such as age, gender, and comorbidity status.

Black patients had higher odds of receiving chemotherapy between 2010 and 2016 compared with 2004 and 2009. “This suggests a positive impact of the Patient Protection and Affordable Care Act (ACA) in 2010,” Dr. Tapan said.

Another surprising finding pertained to patients with nonprivate insurance. These patients had even lower odds of getting chemotherapy after the implementation of ACA, Dr. Tapan said. Patients who had private insurance had higher survival compared with those who were uninsured.

Higher level of education, measured by percentage of residents with a high school degree, increased the odds of receiving chemotherapy.

Age also had a significant impact on receipt of chemotherapy. About 83% of patients over age 80 years received chemotherapy, compared with 94% of patients aged 40-64 years.
 

Real-world data

Minorities are underrepresented in cancer clinical trials in the United States, with only 2% of National Cancer Institute trials having sufficient minority participants, Dr. Tapan said. A study published in Academic Medicine in 2018 showed that only 13% of 782 National Institute of Health–sponsored clinical trials reported outcomes by race and ethnicity.

As a result, we are missing data on patient care in minority populations, Dr. Tapan said. “Collecting and analyzing real-world data becomes critical to study treatment patterns and outcomes,” he added.

The current real-world study had a somewhat diverse patient population, but 90.6% of patients were White, 7.8% were Black, and 1.7% were other races.

“We would have expected a higher percentage of Black patients considering the most recent U.S. Census Bureau estimates that 76.3% of the U.S. population is White and 13.4% is Black,” Dr. Tapan said. “There are conflicting results in the literature regarding racial disparities in SCLC and survival. Many of these studies were performed via state-based cancer registries instead of on a national level, making prior reports less generalizable.”
 

‘More work to do’

While the new study showed patients with nonprivate insurance or those with no insurance were less likely to receive chemotherapy, studies have shown that chemotherapy administration was not impacted by insurance status in limited-stage SCLC.

This is in contrast to radiotherapy delivery. Studies have revealed a lower likelihood of radiotherapy delivery in limited-stage SCLC for patients with government health insurance such as Medicare/Medicaid, Dr. Tapan said.

“Access to cancer care has been shown to be one of the most important barriers in racial disparity. Studies analyzing outcomes in the equal access health systems, such as the Veteran Administration, have revealed less racial disparities,” Dr. Tapan said.

Even when Black patients have equal access to care, they might receive suboptimal treatment, Dr. Tapan noted.

“Studies have shown that Black patients are not only more likely to refuse surgery, but also are more likely to be given a negative recommendation by a surgeon as compared to Whites, suggesting potential involvement of miscommunication or bias during patient-physician encounters,” Dr. Tapan said. “In the same vein, physicians would need to acknowledge their patients’ beliefs. Not doing so may lead to unsatisfactory physician-patient interactions and suboptimal decision-making.”

“Measures to reduce physician bias are an important step to reduce disparities,” Dr. Tapan continued. “Studies have shown that Black patients are perceived to be less intelligent and educated, less likely to have social support, and more likely to be at risk of noncompliance. For some patients and oncologists, extra effort is needed so that every patient can access the best possible treatments and outcomes. It is the oncologist’s responsibility to advocate for patients, but, ultimately, further legislative actions are needed to mitigate the disparities around cancer care.”

Dr. Tapan noted that, in 1966, Martin Luther King Jr., PhD, stated that “of all the forms of inequality, injustice in health care is the most shocking and inhumane.”

Dr. Tapan said: “We have overcome some barriers since 1966, but we have more work to do.” He and colleagues had no disclosures related to this study.

SOURCE: Tapan U et al. JTO Clin Res Rep. 2020. doi: 10.1016/j.jtocrr.2020.100109.

Cancer drug approvals between 2000 and 2016 were associated with a significant reduction in deaths from the most common cancers in the United States, according to a new study.

Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.

A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.

The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.

“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.

The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.

“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
 

Full effect not yet observed

The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.

The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.

The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.

Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).

Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.

The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.

“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
 

Other factors at play

Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”  

Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.

“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”  

Cancer screening is not as strong an influence as it should be, Dr. Cance said.

“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.

More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.

“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”

“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”

“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”

Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.

SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.

Cancer drug approvals between 2000 and 2016 were associated with a significant reduction in deaths from the most common cancers in the United States, according to a new study.

Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.

A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.

The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.

“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.

The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.

“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
 

Full effect not yet observed

The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.

The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.

The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.

Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).

Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.

The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.

“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
 

Other factors at play

Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”  

Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.

“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”  

Cancer screening is not as strong an influence as it should be, Dr. Cance said.

“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.

More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.

“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”

“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”

“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”

Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.

SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.

Cancer drug approvals between 2000 and 2016 were associated with a significant reduction in deaths from the most common cancers in the United States, according to a new study.

Reductions in mortality were most notable for tumor types with relatively more approvals, including lung and breast cancer, melanoma, lymphoma, and leukemia.

A report from the American Cancer Society (ACS) estimated that, from 1991 to 2017, there were 2,902,200 total cancer deaths avoided from improvements in mortality from all potential sources.

The new findings, reported in the Journal of Medical Economics, suggest that drugs approved between 2000 and 2016 to treat the 15 most common cancer types helped to reduce mortality by 24% per 100,000 people.

“This study provides evidence that a significant share of that reduction from 2000 to 2016 was associated with the introduction of new therapies. The ACS report and other studies demonstrate that the improvements in lung cancer specifically are likely due to new treatments,” said lead study author Joanna P. MacEwan, MD, of PRECISIONheor in Los Angeles.

The findings contribute to a better understanding of whether increased spending on cancer drugs are worth the investment, according to the study authors.

“We provide evidence that the gains in survival measured in clinical trials are translating into health benefits for patients in the real world and confirm previous research that has also shown that new pharmaceutical treatments are associated with improved real-world survival outcomes for patients,” Dr. MacEwan said.
 

Full effect not yet observed

The researchers used a series of national data sets from sources including the Centers for Disease Control and Prevention; the U.S. Mortality Files by the National Center of Health Statistics; Survival, Epidemiology and End Results program; and United States Cancer Statistics.

The team calculated age-adjusted cancer mortality rates per year for the 15 most common tumor types and also looked at incident cases of cancer by tumor type, represented as per 100,000 people, for all ages, races, and genders.

The researchers then translated the change in cancer mortality in the U.S. from 2000 to 2016 associated with treatment stocks in each year into deaths averted per year.

Across the 16 years, mortality was down by 1,291,769 deaths. The following cancers had significant reductions in mortality: breast (n = 127,874), colorectal (n = 46,705), lung (n = 375,256), prostate (n = 476,210), gastric (n = 758), and renal (n = 739) cancers, as well as non-Hodgkin lymphoma (n = 48,836) and leukemia (n = 4,011).

Estimated mortality increased by 825 deaths in patients with thyroid cancer and 7,768 deaths for those with bladder cancer. These rises are likely due to the result of sparse drug approvals during this period – five for thyroid cancer and three for bladder cancer – Dr. MacEwan said. There were no approvals in liver or uterine cancer and few approvals in pancreatic and oral cancer.

The full effect of new drug introductions may not have been observed yet, Dr. MacEwan noted.

“There are fewer patients using the treatments for drugs approved in the later years of our study and less follow-up time to measure outcomes,” she said. “Over time, utilization of the newer therapies will likely increase and the full effect on mortality will be observed.”
 

Other factors at play

Multiple factors have led to the declines in mortality, said William G. Cance, MD, chief medical and scientific officer for the ACS, who was not involved in this study. “We are slowly sorting out the explanations in greater granularity.”  

Dr. MacEwan said improved cancer screening may partially explain the decline in mortality in some tumor types.

“If screening in a particular tumor type improved during the study period and tumors were diagnosed earlier, then mortality for that tumor type may decline,” she said. “However, we did not find strong evidence to suggest that there were significant changes in screening during our study period. Breast cancer screening rates, for example, were stable over our study period.”  

Cancer screening is not as strong an influence as it should be, Dr. Cance said.

“The lung cancer screening rate is low. In breast and colorectal cancers, we need to double down on earlier screening,” he said, noting that less than one-quarter of adults between ages 45 and 50 years are currently screened for colorectal cancer. The ACS recommends that people at average risk of colorectal cancer start regular screening at age 45.

More research is necessary to evaluate the relationship between drug approvals and cancer mortality, Dr. MacEwan said.

“Research directly linking utilization of new therapies to improved survival or reduced mortality in the real-world setting would more definitively demonstrate the impact of new treatments,” she said. “New therapies have improved outcomes for many patients and should continue to be considered as key elements of cancer treatment.”

“We need to continue to reduce tobacco smoking and improve on modifiable behaviors at the same time as we work on getting new drugs to cancer patients,” Dr. Cance said. “We are coming into an era of multiple new therapeutics, including targeted therapies, immunotherapies, and cellular therapies. Clinicians need to look closely at the trial data of new drugs and pay close attention to those that have the most mortality impact.”

“We also need equitable distribution of newer drugs,” Dr. Cance added. “They should be distributed to everybody who deserves them. Mortality is often impacted by social determinants of health.”

Funding for this research was provided by Pfizer. Study authors disclosed relationships, including employment, with Pfizer. Dr. Cance had no disclosures.

SOURCE: MacEwan JP et al. J Med Econ. 2020 Nov 9;1-12.

Real-world survival outcomes for cancer patients on immune checkpoint inhibitors (ICIs) are inferior to outcomes reported in patients on clinical trials of ICIs, according to research published in JCO Clinical Cancer Informatics.

However, the research also suggests that real-world patients who receive ICIs achieve longer survival than patients on standard-of-care medications.

“Patients receiving ICIs in real-world practice may differ from those enrolled in trials in a variety of ways, including age, race, performance status, and comorbidity burden,” said study author Jerry S.H. Lee, PhD, of the University of Southern California, Los Angeles.

Dr. Lee noted that only 3%-4% of cancer patients participate in clinical trials. In fact, more than half of patients with melanoma and nearly three-quarters of those with non–small cell lung cancer (NSCLC) do not meet criteria for eligibility in clinical trials, he said.

To examine the discrepancies between real-world practice and clinical trials and to better understand which patients receive ICIs in clinical practice, Dr. Lee and colleagues conducted a retrospective analysis using electronic health record data from Veterans Administration (VA) facilities nationwide.

The researchers identified 11,888 cancer patients who were treated with ICIs. The cohort included patients who are underrepresented in pivotal clinical trials, including older, non-White, and/or higher disease-burdened patients.

The majority of patients were treated for NSCLC (51.1%), followed by melanoma (14.4%), renal cell carcinoma (RCC; 8.1%), squamous cell carcinoma of the head and neck (6.8%), urothelial cancer (6.4%), hepatocellular carcinoma (4.5%), and other less common cancer types (8.8%).
 

Overall survival by indication

In general, median overall survival (OS) in the VA cohort was inferior to median OS reported in clinical trials. However, patients treated with first-line nivolumab for melanoma and second-line pembrolizumab or nivolumab for NSCLC had similar OS in the real-world and trial data.

The researchers did not report exact OS numbers from clinical trials. However, they did report the exact numbers from the VA cohort and show OS differences between the VA cohort and clinical trials graphically.

Among patients in the VA cohort, the median OS was:

• 25.5 months in melanoma patients on first-line nivolumab
• 16.3 months in RCC patients receiving nivolumab in the second line or higher
• 14 months in RCC patients on first-line ipilimumab and nivolumab
• 10.6 months in NSCLC patients on first-line pembrolizumab
• 9.9 months in NSCLC patients receiving pembrolizumab or nivolumab in the second line or higher
• 9.1 months in NSCLC patients on first-line pembrolizumab and platinum-based chemotherapy
• 6.7 months in urothelial cancer patients receiving ICIs in the second line or higher.

A number of factors may have contributed to the shorter OS observed in the VA cohort, according to the researchers. The VA cohort is predominantly male, is older, and has a higher degree of comorbidity, compared with patients in clinical trials.

In addition, no data are available to determine the cause for discontinuation of therapy, and VA patients may have received ICIs after failing multiple lines of previous therapy, while clinical trials may limit patients to only one or two previous lines of therapy.

After stratifying VA patients by frailty status, the OS among non-frail patients was more similar to the OS reported in clinical trials.

“Real-world outcomes from the VA were more similar when adjusted for frailty, which shows the importance of patient diversity in clinical trials,” Dr. Lee said. He added that the definition of frailty among VA patients included potential injury during combat and therefore differs from a generic frailty definition.
 

ICIs vs. standard care

The researchers also found that VA patients treated with ICIs had longer OS, compared with a cohort of VA patients receiving standard-of-care therapies.

The median OS was as follows:

• In melanoma patients on first-line treatment – 39.29 months with nivolumab and 5.75 months with chemotherapy (P < .001).
• In RCC patients on first-line treatment – 14.01 months with ipilimumab plus nivolumab and 8.63 months with targeted therapy (P = .051).
• In RCC patients on second-line or greater treatment – 12.43 months with nivolumab and 8.09 months with everolimus (P < .001).
• In NSCLC patients on first-line therapy – 8.88 months with pembrolizumab and 6.38 months with a platinum doublet (P < .001).
• In NSCLC patients on first-line combination therapy – 10.59 months with pembrolizumab plus platinum chemotherapy and 6.38 months with a platinum doublet (P < .001).
• In NSCLC patients on second-line or greater therapy – 10.06 months with pembrolizumab or nivolumab and 6.41 months with docetaxel (P < .001).
• In urothelial cancer patients on second-line or greater therapy – 7.66 months with an ICI and 6.31 months with chemotherapy (P = .043).
   

Help for treatment decisions

“The real-world survival outcomes not only indicate the breadth of indications but also represent patients who tend not to be eligible for immunotherapy trials, based on their health status,” Dr. Lee said. “We hope this dataset of national-level experience provides practicing oncologists evidence to help patients and family members in the process of decision-making about therapy.”

Real-world data can also inform oncologists who face decisions on whether to prescribe or withhold ICIs and patients who face the financial burden of paying for ICIs, he said.

This dataset will be continually updated. The researchers have already added another 10,000 VA patients who have received immunotherapies in the year since the trial began.

“In a longitudinal way, we plan to examine what causes differences in outcomes and continue to find ways to extend care to veterans with a balance of high quality of life,” Dr. Lee said.

“Patients who participate in clinical trials are, on average, younger and healthier than the general population,” said Bora Youn, PhD, a senior biostatistician at Biogen in Cambridge, Mass., who was not involved in this study.

“In the case of immunotherapies, those with poor performance status and autoimmune conditions are often excluded from trials,” Dr. Youn added. “In the real world, these patients can also receive treatments, and clinicians often need to extrapolate the results from clinical trials. It is therefore important to collect real-world data to understand the effectiveness and safety of these therapies in patients with limited evidence.”

Dr. Youn led a real-world study, published in Cancer, of 1,256 Medicare recipients who were diagnosed with NSCLC and received ICI therapy.

“We found that factors associated with poor prognosis in general, such as squamous histology and failure of aggressive prior treatment, are also predictive of decreased survival among those who initiated immunotherapies. Yet, OS of older patients was relatively comparable to those observed in clinical trials,” Dr. Youn said.

“Understanding the real-world effectiveness of these treatments will help improve the evidence base, especially for those underrepresented in clinical trials. These studies can also help identify patients who are most likely to benefit from immunotherapies,” Dr. Youn added.

This study was supported by the VA Office of Research and Development Cooperative Studies Program. Dr. Lee and Dr. Youn disclosed no conflicts of interest.

SOURCE: Jennifer La et al. JCO Clinical Cancer Informatics. 2020:4:918-28.

Real-world survival outcomes for cancer patients on immune checkpoint inhibitors (ICIs) are inferior to outcomes reported in patients on clinical trials of ICIs, according to research published in JCO Clinical Cancer Informatics.

However, the research also suggests that real-world patients who receive ICIs achieve longer survival than patients on standard-of-care medications.

“Patients receiving ICIs in real-world practice may differ from those enrolled in trials in a variety of ways, including age, race, performance status, and comorbidity burden,” said study author Jerry S.H. Lee, PhD, of the University of Southern California, Los Angeles.

Dr. Lee noted that only 3%-4% of cancer patients participate in clinical trials. In fact, more than half of patients with melanoma and nearly three-quarters of those with non–small cell lung cancer (NSCLC) do not meet criteria for eligibility in clinical trials, he said.

To examine the discrepancies between real-world practice and clinical trials and to better understand which patients receive ICIs in clinical practice, Dr. Lee and colleagues conducted a retrospective analysis using electronic health record data from Veterans Administration (VA) facilities nationwide.

The researchers identified 11,888 cancer patients who were treated with ICIs. The cohort included patients who are underrepresented in pivotal clinical trials, including older, non-White, and/or higher disease-burdened patients.

The majority of patients were treated for NSCLC (51.1%), followed by melanoma (14.4%), renal cell carcinoma (RCC; 8.1%), squamous cell carcinoma of the head and neck (6.8%), urothelial cancer (6.4%), hepatocellular carcinoma (4.5%), and other less common cancer types (8.8%).
 

Overall survival by indication

In general, median overall survival (OS) in the VA cohort was inferior to median OS reported in clinical trials. However, patients treated with first-line nivolumab for melanoma and second-line pembrolizumab or nivolumab for NSCLC had similar OS in the real-world and trial data.

The researchers did not report exact OS numbers from clinical trials. However, they did report the exact numbers from the VA cohort and show OS differences between the VA cohort and clinical trials graphically.

Among patients in the VA cohort, the median OS was:

• 25.5 months in melanoma patients on first-line nivolumab
• 16.3 months in RCC patients receiving nivolumab in the second line or higher
• 14 months in RCC patients on first-line ipilimumab and nivolumab
• 10.6 months in NSCLC patients on first-line pembrolizumab
• 9.9 months in NSCLC patients receiving pembrolizumab or nivolumab in the second line or higher
• 9.1 months in NSCLC patients on first-line pembrolizumab and platinum-based chemotherapy
• 6.7 months in urothelial cancer patients receiving ICIs in the second line or higher.

A number of factors may have contributed to the shorter OS observed in the VA cohort, according to the researchers. The VA cohort is predominantly male, is older, and has a higher degree of comorbidity, compared with patients in clinical trials.

In addition, no data are available to determine the cause for discontinuation of therapy, and VA patients may have received ICIs after failing multiple lines of previous therapy, while clinical trials may limit patients to only one or two previous lines of therapy.

After stratifying VA patients by frailty status, the OS among non-frail patients was more similar to the OS reported in clinical trials.

“Real-world outcomes from the VA were more similar when adjusted for frailty, which shows the importance of patient diversity in clinical trials,” Dr. Lee said. He added that the definition of frailty among VA patients included potential injury during combat and therefore differs from a generic frailty definition.
 

ICIs vs. standard care

The researchers also found that VA patients treated with ICIs had longer OS, compared with a cohort of VA patients receiving standard-of-care therapies.

The median OS was as follows:

• In melanoma patients on first-line treatment – 39.29 months with nivolumab and 5.75 months with chemotherapy (P < .001).
• In RCC patients on first-line treatment – 14.01 months with ipilimumab plus nivolumab and 8.63 months with targeted therapy (P = .051).
• In RCC patients on second-line or greater treatment – 12.43 months with nivolumab and 8.09 months with everolimus (P < .001).
• In NSCLC patients on first-line therapy – 8.88 months with pembrolizumab and 6.38 months with a platinum doublet (P < .001).
• In NSCLC patients on first-line combination therapy – 10.59 months with pembrolizumab plus platinum chemotherapy and 6.38 months with a platinum doublet (P < .001).
• In NSCLC patients on second-line or greater therapy – 10.06 months with pembrolizumab or nivolumab and 6.41 months with docetaxel (P < .001).
• In urothelial cancer patients on second-line or greater therapy – 7.66 months with an ICI and 6.31 months with chemotherapy (P = .043).
   

Help for treatment decisions

“The real-world survival outcomes not only indicate the breadth of indications but also represent patients who tend not to be eligible for immunotherapy trials, based on their health status,” Dr. Lee said. “We hope this dataset of national-level experience provides practicing oncologists evidence to help patients and family members in the process of decision-making about therapy.”

Real-world data can also inform oncologists who face decisions on whether to prescribe or withhold ICIs and patients who face the financial burden of paying for ICIs, he said.

This dataset will be continually updated. The researchers have already added another 10,000 VA patients who have received immunotherapies in the year since the trial began.

“In a longitudinal way, we plan to examine what causes differences in outcomes and continue to find ways to extend care to veterans with a balance of high quality of life,” Dr. Lee said.

“Patients who participate in clinical trials are, on average, younger and healthier than the general population,” said Bora Youn, PhD, a senior biostatistician at Biogen in Cambridge, Mass., who was not involved in this study.

“In the case of immunotherapies, those with poor performance status and autoimmune conditions are often excluded from trials,” Dr. Youn added. “In the real world, these patients can also receive treatments, and clinicians often need to extrapolate the results from clinical trials. It is therefore important to collect real-world data to understand the effectiveness and safety of these therapies in patients with limited evidence.”

Dr. Youn led a real-world study, published in Cancer, of 1,256 Medicare recipients who were diagnosed with NSCLC and received ICI therapy.

“We found that factors associated with poor prognosis in general, such as squamous histology and failure of aggressive prior treatment, are also predictive of decreased survival among those who initiated immunotherapies. Yet, OS of older patients was relatively comparable to those observed in clinical trials,” Dr. Youn said.

“Understanding the real-world effectiveness of these treatments will help improve the evidence base, especially for those underrepresented in clinical trials. These studies can also help identify patients who are most likely to benefit from immunotherapies,” Dr. Youn added.

This study was supported by the VA Office of Research and Development Cooperative Studies Program. Dr. Lee and Dr. Youn disclosed no conflicts of interest.

SOURCE: Jennifer La et al. JCO Clinical Cancer Informatics. 2020:4:918-28.

Real-world survival outcomes for cancer patients on immune checkpoint inhibitors (ICIs) are inferior to outcomes reported in patients on clinical trials of ICIs, according to research published in JCO Clinical Cancer Informatics.

However, the research also suggests that real-world patients who receive ICIs achieve longer survival than patients on standard-of-care medications.

“Patients receiving ICIs in real-world practice may differ from those enrolled in trials in a variety of ways, including age, race, performance status, and comorbidity burden,” said study author Jerry S.H. Lee, PhD, of the University of Southern California, Los Angeles.

Dr. Lee noted that only 3%-4% of cancer patients participate in clinical trials. In fact, more than half of patients with melanoma and nearly three-quarters of those with non–small cell lung cancer (NSCLC) do not meet criteria for eligibility in clinical trials, he said.

To examine the discrepancies between real-world practice and clinical trials and to better understand which patients receive ICIs in clinical practice, Dr. Lee and colleagues conducted a retrospective analysis using electronic health record data from Veterans Administration (VA) facilities nationwide.

The researchers identified 11,888 cancer patients who were treated with ICIs. The cohort included patients who are underrepresented in pivotal clinical trials, including older, non-White, and/or higher disease-burdened patients.

The majority of patients were treated for NSCLC (51.1%), followed by melanoma (14.4%), renal cell carcinoma (RCC; 8.1%), squamous cell carcinoma of the head and neck (6.8%), urothelial cancer (6.4%), hepatocellular carcinoma (4.5%), and other less common cancer types (8.8%).
 

Overall survival by indication

In general, median overall survival (OS) in the VA cohort was inferior to median OS reported in clinical trials. However, patients treated with first-line nivolumab for melanoma and second-line pembrolizumab or nivolumab for NSCLC had similar OS in the real-world and trial data.

The researchers did not report exact OS numbers from clinical trials. However, they did report the exact numbers from the VA cohort and show OS differences between the VA cohort and clinical trials graphically.

Among patients in the VA cohort, the median OS was:

• 25.5 months in melanoma patients on first-line nivolumab
• 16.3 months in RCC patients receiving nivolumab in the second line or higher
• 14 months in RCC patients on first-line ipilimumab and nivolumab
• 10.6 months in NSCLC patients on first-line pembrolizumab
• 9.9 months in NSCLC patients receiving pembrolizumab or nivolumab in the second line or higher
• 9.1 months in NSCLC patients on first-line pembrolizumab and platinum-based chemotherapy
• 6.7 months in urothelial cancer patients receiving ICIs in the second line or higher.

A number of factors may have contributed to the shorter OS observed in the VA cohort, according to the researchers. The VA cohort is predominantly male, is older, and has a higher degree of comorbidity, compared with patients in clinical trials.

In addition, no data are available to determine the cause for discontinuation of therapy, and VA patients may have received ICIs after failing multiple lines of previous therapy, while clinical trials may limit patients to only one or two previous lines of therapy.

After stratifying VA patients by frailty status, the OS among non-frail patients was more similar to the OS reported in clinical trials.

“Real-world outcomes from the VA were more similar when adjusted for frailty, which shows the importance of patient diversity in clinical trials,” Dr. Lee said. He added that the definition of frailty among VA patients included potential injury during combat and therefore differs from a generic frailty definition.
 

ICIs vs. standard care

The researchers also found that VA patients treated with ICIs had longer OS, compared with a cohort of VA patients receiving standard-of-care therapies.

The median OS was as follows:

• In melanoma patients on first-line treatment – 39.29 months with nivolumab and 5.75 months with chemotherapy (P < .001).
• In RCC patients on first-line treatment – 14.01 months with ipilimumab plus nivolumab and 8.63 months with targeted therapy (P = .051).
• In RCC patients on second-line or greater treatment – 12.43 months with nivolumab and 8.09 months with everolimus (P < .001).
• In NSCLC patients on first-line therapy – 8.88 months with pembrolizumab and 6.38 months with a platinum doublet (P < .001).
• In NSCLC patients on first-line combination therapy – 10.59 months with pembrolizumab plus platinum chemotherapy and 6.38 months with a platinum doublet (P < .001).
• In NSCLC patients on second-line or greater therapy – 10.06 months with pembrolizumab or nivolumab and 6.41 months with docetaxel (P < .001).
• In urothelial cancer patients on second-line or greater therapy – 7.66 months with an ICI and 6.31 months with chemotherapy (P = .043).
   

Help for treatment decisions

“The real-world survival outcomes not only indicate the breadth of indications but also represent patients who tend not to be eligible for immunotherapy trials, based on their health status,” Dr. Lee said. “We hope this dataset of national-level experience provides practicing oncologists evidence to help patients and family members in the process of decision-making about therapy.”

Real-world data can also inform oncologists who face decisions on whether to prescribe or withhold ICIs and patients who face the financial burden of paying for ICIs, he said.

This dataset will be continually updated. The researchers have already added another 10,000 VA patients who have received immunotherapies in the year since the trial began.

“In a longitudinal way, we plan to examine what causes differences in outcomes and continue to find ways to extend care to veterans with a balance of high quality of life,” Dr. Lee said.

“Patients who participate in clinical trials are, on average, younger and healthier than the general population,” said Bora Youn, PhD, a senior biostatistician at Biogen in Cambridge, Mass., who was not involved in this study.

“In the case of immunotherapies, those with poor performance status and autoimmune conditions are often excluded from trials,” Dr. Youn added. “In the real world, these patients can also receive treatments, and clinicians often need to extrapolate the results from clinical trials. It is therefore important to collect real-world data to understand the effectiveness and safety of these therapies in patients with limited evidence.”

Dr. Youn led a real-world study, published in Cancer, of 1,256 Medicare recipients who were diagnosed with NSCLC and received ICI therapy.

“We found that factors associated with poor prognosis in general, such as squamous histology and failure of aggressive prior treatment, are also predictive of decreased survival among those who initiated immunotherapies. Yet, OS of older patients was relatively comparable to those observed in clinical trials,” Dr. Youn said.

“Understanding the real-world effectiveness of these treatments will help improve the evidence base, especially for those underrepresented in clinical trials. These studies can also help identify patients who are most likely to benefit from immunotherapies,” Dr. Youn added.

This study was supported by the VA Office of Research and Development Cooperative Studies Program. Dr. Lee and Dr. Youn disclosed no conflicts of interest.

SOURCE: Jennifer La et al. JCO Clinical Cancer Informatics. 2020:4:918-28.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

All breast cancer patients who develop a second primary cancer should undergo multigene panel testing, according to a paper published in JCO Precision Oncology.

The authors noted that women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. However, it hasn’t been clear if mutations in genes other than BRCA1/2 are enriched in patients with multiple primary cancers.

“Surprisingly few papers have focused on genetic evaluation of patients with multiple primary cancers,” senior author Katherine L. Nathanson, MD, of the University of Pennsylvania in Philadelphia, said in an interview.

“Ours is one of the first studies to look closely at this issue. We know from clinical experience that these patients are more likely to have more than one genetic mutation,” she added.

For their study, Dr. Nathanson and colleagues identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in two cohorts.

Cohort 1 consisted of 1,000 high-risk breast cancer patients – 551 with multiple primary cancers and 449 with a single breast cancer.

Cohort 2 included 1,804 familial breast cancer patients – 340 with multiple primaries and 1,464 with a single breast cancer.

The researchers assessed mutations in these cohorts and compared them with mutations in a control data set.
 

Mutation rates and age

Pathogenic mutation rates were higher in both cohorts in patients with multiple primaries as compared with patients with single primaries.

In cohort 1, the overall panel positive rate was 8.53% in the multiple-primaries group and 4.90% in the single-primary group (P = .024).

In cohort 2, the overall panel positive rate was 7.06% in the multiple-primaries group and 4.23% in the single-primary group (P = .034).

In both cohorts, younger age at first breast cancer was associated with higher mutation rates. However, the age at onset of cancers other than breast cancer was not related to mutation rate.

“Regardless of age, mutations in genes other than BRCA1/2 are found in at least 5% of patients with breast cancer and another primary cancer, with up to 25% in patients with their first breast cancer at age 30 years,” Dr. Nathanson said. “This supports the need for multigene panel testing in all patients with breast cancer and another primary cancer.”

“Once a woman has multiple primaries with breast cancer, it doesn’t matter what her family history is, she is more likely to be at risk,” Dr. Nathanson added.
 

Genetic susceptibility

The researchers also identified genes associated with multiple primary cancers. TP53 and MSH6 mutations were significantly enriched in patients with multiple primaries but not single primaries. ATM and PALB2 mutations were significantly enriched in both groups when compared with controls.

The researchers noted that high-penetrance cancer genes were responsible for higher mutation rates in the cohort enriched for early-onset breast cancer and non–breast cancer second primaries. Moderate-penetrance cancer genes were responsible for the higher mutation rates in the cohort enriched for familial breast cancer and second breast cancer primaries.

“In multiple primary cancers, we found additional genes with moderate penetrance and some genes with high penetrance associated with TP53 and Lynch syndrome,” Dr. Nathanson said.
 

Cancer prevention and screening

The results of this study could lead to better implementation of cancer prevention and screening strategies, according to the researchers.

“As we look at guidelines in development and NCCN recommendations, our data suggest that age should not be part of the criteria for genetic testing in patients who have more than one primary cancer. These patients are at high risk and should be recommended for screening,” Dr. Nathanson said.

“If you see a patient with multiple primary cancers, refer for genetic testing. Age does not matter,” she reiterated.

Future research will look at potentially missing mutations.

“With targeted sequencing, structurally rearranged genes might be missed for those at risk. We will try to identify cancer susceptibility genes and define the true risk of penetrance of these genes in the general population,” Dr. Nathanson said.

This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Dr. Nathanson disclosed no conflicts of interest. Other authors disclosed relationships with a range of companies, all listed in the paper.

SOURCE: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.

All breast cancer patients who develop a second primary cancer should undergo multigene panel testing, according to a paper published in JCO Precision Oncology.

The authors noted that women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. However, it hasn’t been clear if mutations in genes other than BRCA1/2 are enriched in patients with multiple primary cancers.

“Surprisingly few papers have focused on genetic evaluation of patients with multiple primary cancers,” senior author Katherine L. Nathanson, MD, of the University of Pennsylvania in Philadelphia, said in an interview.

“Ours is one of the first studies to look closely at this issue. We know from clinical experience that these patients are more likely to have more than one genetic mutation,” she added.

For their study, Dr. Nathanson and colleagues identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in two cohorts.

Cohort 1 consisted of 1,000 high-risk breast cancer patients – 551 with multiple primary cancers and 449 with a single breast cancer.

Cohort 2 included 1,804 familial breast cancer patients – 340 with multiple primaries and 1,464 with a single breast cancer.

The researchers assessed mutations in these cohorts and compared them with mutations in a control data set.
 

Mutation rates and age

Pathogenic mutation rates were higher in both cohorts in patients with multiple primaries as compared with patients with single primaries.

In cohort 1, the overall panel positive rate was 8.53% in the multiple-primaries group and 4.90% in the single-primary group (P = .024).

In cohort 2, the overall panel positive rate was 7.06% in the multiple-primaries group and 4.23% in the single-primary group (P = .034).

In both cohorts, younger age at first breast cancer was associated with higher mutation rates. However, the age at onset of cancers other than breast cancer was not related to mutation rate.

“Regardless of age, mutations in genes other than BRCA1/2 are found in at least 5% of patients with breast cancer and another primary cancer, with up to 25% in patients with their first breast cancer at age 30 years,” Dr. Nathanson said. “This supports the need for multigene panel testing in all patients with breast cancer and another primary cancer.”

“Once a woman has multiple primaries with breast cancer, it doesn’t matter what her family history is, she is more likely to be at risk,” Dr. Nathanson added.
 

Genetic susceptibility

The researchers also identified genes associated with multiple primary cancers. TP53 and MSH6 mutations were significantly enriched in patients with multiple primaries but not single primaries. ATM and PALB2 mutations were significantly enriched in both groups when compared with controls.

The researchers noted that high-penetrance cancer genes were responsible for higher mutation rates in the cohort enriched for early-onset breast cancer and non–breast cancer second primaries. Moderate-penetrance cancer genes were responsible for the higher mutation rates in the cohort enriched for familial breast cancer and second breast cancer primaries.

“In multiple primary cancers, we found additional genes with moderate penetrance and some genes with high penetrance associated with TP53 and Lynch syndrome,” Dr. Nathanson said.
 

Cancer prevention and screening

The results of this study could lead to better implementation of cancer prevention and screening strategies, according to the researchers.

“As we look at guidelines in development and NCCN recommendations, our data suggest that age should not be part of the criteria for genetic testing in patients who have more than one primary cancer. These patients are at high risk and should be recommended for screening,” Dr. Nathanson said.

“If you see a patient with multiple primary cancers, refer for genetic testing. Age does not matter,” she reiterated.

Future research will look at potentially missing mutations.

“With targeted sequencing, structurally rearranged genes might be missed for those at risk. We will try to identify cancer susceptibility genes and define the true risk of penetrance of these genes in the general population,” Dr. Nathanson said.

This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Dr. Nathanson disclosed no conflicts of interest. Other authors disclosed relationships with a range of companies, all listed in the paper.

SOURCE: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.

All breast cancer patients who develop a second primary cancer should undergo multigene panel testing, according to a paper published in JCO Precision Oncology.

The authors noted that women with breast cancer have a 4%-16% lifetime risk of a second primary cancer. However, it hasn’t been clear if mutations in genes other than BRCA1/2 are enriched in patients with multiple primary cancers.

“Surprisingly few papers have focused on genetic evaluation of patients with multiple primary cancers,” senior author Katherine L. Nathanson, MD, of the University of Pennsylvania in Philadelphia, said in an interview.

“Ours is one of the first studies to look closely at this issue. We know from clinical experience that these patients are more likely to have more than one genetic mutation,” she added.

For their study, Dr. Nathanson and colleagues identified pathogenic germline mutations in 17 cancer susceptibility genes in patients with BRCA1/2-negative breast cancer in two cohorts.

Cohort 1 consisted of 1,000 high-risk breast cancer patients – 551 with multiple primary cancers and 449 with a single breast cancer.

Cohort 2 included 1,804 familial breast cancer patients – 340 with multiple primaries and 1,464 with a single breast cancer.

The researchers assessed mutations in these cohorts and compared them with mutations in a control data set.
 

Mutation rates and age

Pathogenic mutation rates were higher in both cohorts in patients with multiple primaries as compared with patients with single primaries.

In cohort 1, the overall panel positive rate was 8.53% in the multiple-primaries group and 4.90% in the single-primary group (P = .024).

In cohort 2, the overall panel positive rate was 7.06% in the multiple-primaries group and 4.23% in the single-primary group (P = .034).

In both cohorts, younger age at first breast cancer was associated with higher mutation rates. However, the age at onset of cancers other than breast cancer was not related to mutation rate.

“Regardless of age, mutations in genes other than BRCA1/2 are found in at least 5% of patients with breast cancer and another primary cancer, with up to 25% in patients with their first breast cancer at age 30 years,” Dr. Nathanson said. “This supports the need for multigene panel testing in all patients with breast cancer and another primary cancer.”

“Once a woman has multiple primaries with breast cancer, it doesn’t matter what her family history is, she is more likely to be at risk,” Dr. Nathanson added.
 

Genetic susceptibility

The researchers also identified genes associated with multiple primary cancers. TP53 and MSH6 mutations were significantly enriched in patients with multiple primaries but not single primaries. ATM and PALB2 mutations were significantly enriched in both groups when compared with controls.

The researchers noted that high-penetrance cancer genes were responsible for higher mutation rates in the cohort enriched for early-onset breast cancer and non–breast cancer second primaries. Moderate-penetrance cancer genes were responsible for the higher mutation rates in the cohort enriched for familial breast cancer and second breast cancer primaries.

“In multiple primary cancers, we found additional genes with moderate penetrance and some genes with high penetrance associated with TP53 and Lynch syndrome,” Dr. Nathanson said.
 

Cancer prevention and screening

The results of this study could lead to better implementation of cancer prevention and screening strategies, according to the researchers.

“As we look at guidelines in development and NCCN recommendations, our data suggest that age should not be part of the criteria for genetic testing in patients who have more than one primary cancer. These patients are at high risk and should be recommended for screening,” Dr. Nathanson said.

“If you see a patient with multiple primary cancers, refer for genetic testing. Age does not matter,” she reiterated.

Future research will look at potentially missing mutations.

“With targeted sequencing, structurally rearranged genes might be missed for those at risk. We will try to identify cancer susceptibility genes and define the true risk of penetrance of these genes in the general population,” Dr. Nathanson said.

This research was supported by grants from government agencies and foundations as well as the University of Pennsylvania. Dr. Nathanson disclosed no conflicts of interest. Other authors disclosed relationships with a range of companies, all listed in the paper.

SOURCE: Maxwell KN et al. JCO Precis Oncol. 2020. doi: 10.1200/PO.19.00301.

A team of U.S. researchers is investigating whether pressurized intraperitoneal aerosolized chemotherapy (PIPAC) can benefit patients with advanced cancer and peritoneal carcinomatosis.

City of Hope

The team’s phase 1 trial is the first in the United States to test PIPAC, and it will enroll patients with ovarian, uterine, colorectal, or gastric cancer who have peritoneal carcinomatosis.

Data from studies outside the United States suggest PIPAC can induce regression of peritoneal carcinomatosis, even in end-stage, therapy-resistant gastric, ovarian, and colorectal cancers (Lancet Oncol. 2019 Jul;20[7]:e368-e377).

The current study (NCT04329494) formally introduces PIPAC to the United States and serves as a launching pad for further investigation into how the treatment should be administered and which types of chemotherapies can be used.
 

About PIPAC

“PIPAC is a novel therapeutic approach that is minimally invasive, does not require cytoreduction, and can be repeated frequently,” said Thanh Dellinger, MD, a gynecologic oncology surgeon at City of Hope in Duarte, Calif., and co–principal investigator of the phase 1 trial.

“[PIPAC] entails accessing the abdominal cavity using standard laparoscopic techniques and relies on the increased intra-abdominal pressure (15 mm Hg) achieved with laparoscopic surgery, which generates a convective flux that forces aerosolized chemotherapy drugs from the peritoneal cavity into the subperitoneal tissue and overcomes the tumor’s interstitial pressure,” Dr. Dellinger explained in an interview.

“The surgical procedure to deliver PIPAC does not typically cause adhesive disease and allows for repeated delivery of intraperitoneal chemotherapy, objective tumor staging, and response assessment,” she noted.

Dr. Dellinger said the advantages of PIPAC include a minimally invasive approach; no debulking surgery required; deeper uptake of drugs in tumor tissues; wider, more effective drug distribution; fewer toxicities caused by lower drug dosage; repeatable administration; and palliation of peritoneal carcinomatosis symptoms, including abdominal bloating and ascites.

PIPAC achieves a deeper peritoneal nodule penetration of several millimeters with cisplatin, compared to less than 1 mm with heated intraoperative peritoneal chemotherapy (HIPEC) and other intraperitoneal methods, according to Amit Merchea, MD, an assistant professor of surgery at the Mayo Clinic in Jacksonville, Fla.

Dr. Merchea performed the first PIPAC procedure in the United States in December 2019.
 

Innovative therapies needed

Peritoneal carcinomatosis is often a late-stage manifestation of abdominal cancers and is usually lethal, Dr. Dellinger said. She noted that systemic chemotherapy in the palliative setting is relatively ineffective in patients with peritoneal carcinomatosis because of pharmacokinetic limitations, poor peritoneal drug uptake, and impaired local drug distribution.

“Innovative, effective therapies are urgently needed for people who have ovarian, uterine, gastric, or colorectal cancer with peritoneal carcinomatosis,” Dr. Dellinger said.

“PIPAC is a novel treatment option that has had very favorable and exciting results,” Dr. Merchea said. “It is a potential option for patients when no other treatment options exist, and it is an avenue to provide hope to patients when often they have none.”

Potential candidates for PIPAC include patients who have peritoneal carcinomatosis, have failed other standard therapies, have more than 6 months’ life expectancy, and are not candidates for cytoreduction with HIPEC. There remains very limited data on the use of PIPAC as a neoadjuvant approach to convert patients who were previously unresectable to resectable disease, Dr. Merchea noted.

“To deliver chemotherapy directly to the tumor under pressure allows PIPAC to better penetrate the peritoneal surface and tumor nodules than traditional approaches, such as HIPEC,” Dr. Merchea said. “And the drug distribution at the tissue level is better than what is often achieved by systemic chemotherapy, but without the systemic effects of chemotherapy, such as hair loss. The treatment gives essentially a real-time, quantitative assessment of response by being able to directly assess the tumor via laparoscopic visualization and repeat biopsy.”

“Importantly, patients who undergo PIPAC don’t notice a decrease in their quality of life, and some patients note improvement, particularly with respect to nausea, vomiting, appetite, fatigue, and constipation,” Dr. Merchea said.
 

Trial details

The phase 1 trial of PIPAC will include a maximum of 24 patients. They will receive treatment every 6 weeks for up to three cycles and be followed for up to 3 years.

Patients with ovarian, uterine, or gastric cancer will undergo PIPAC with cisplatin, followed by doxorubicin. Patients with colorectal cancer will undergo PIPAC with oxaliplatin preceded by leucovorin and fluorouracil for cycles 2 and 3.

The researchers also plan to profile patients’ tumors.

“Tumor samples will be chronologically evaluated with genomics, spatial transcriptomics, pharmacodynamics, and single-cell sequencing throughout a patient’s treatment course, thus elucidating the treatment effects and natural history of peritoneal cancers,” Dr. Dellinger said.

The trial sites include City of Hope, Mayo Clinic in Florida, Northwell Health in New York, and the National Cancer Institute in Maryland.

The trial is sponsored by City of Hope in collaboration with the National Cancer Institute. Dr. Merchea and Dr. Dellinger reported having no conflicts of interest.

A team of U.S. researchers is investigating whether pressurized intraperitoneal aerosolized chemotherapy (PIPAC) can benefit patients with advanced cancer and peritoneal carcinomatosis.

City of Hope

The team’s phase 1 trial is the first in the United States to test PIPAC, and it will enroll patients with ovarian, uterine, colorectal, or gastric cancer who have peritoneal carcinomatosis.

Data from studies outside the United States suggest PIPAC can induce regression of peritoneal carcinomatosis, even in end-stage, therapy-resistant gastric, ovarian, and colorectal cancers (Lancet Oncol. 2019 Jul;20[7]:e368-e377).

The current study (NCT04329494) formally introduces PIPAC to the United States and serves as a launching pad for further investigation into how the treatment should be administered and which types of chemotherapies can be used.
 

About PIPAC

“PIPAC is a novel therapeutic approach that is minimally invasive, does not require cytoreduction, and can be repeated frequently,” said Thanh Dellinger, MD, a gynecologic oncology surgeon at City of Hope in Duarte, Calif., and co–principal investigator of the phase 1 trial.

“[PIPAC] entails accessing the abdominal cavity using standard laparoscopic techniques and relies on the increased intra-abdominal pressure (15 mm Hg) achieved with laparoscopic surgery, which generates a convective flux that forces aerosolized chemotherapy drugs from the peritoneal cavity into the subperitoneal tissue and overcomes the tumor’s interstitial pressure,” Dr. Dellinger explained in an interview.

“The surgical procedure to deliver PIPAC does not typically cause adhesive disease and allows for repeated delivery of intraperitoneal chemotherapy, objective tumor staging, and response assessment,” she noted.

Dr. Dellinger said the advantages of PIPAC include a minimally invasive approach; no debulking surgery required; deeper uptake of drugs in tumor tissues; wider, more effective drug distribution; fewer toxicities caused by lower drug dosage; repeatable administration; and palliation of peritoneal carcinomatosis symptoms, including abdominal bloating and ascites.

PIPAC achieves a deeper peritoneal nodule penetration of several millimeters with cisplatin, compared to less than 1 mm with heated intraoperative peritoneal chemotherapy (HIPEC) and other intraperitoneal methods, according to Amit Merchea, MD, an assistant professor of surgery at the Mayo Clinic in Jacksonville, Fla.

Dr. Merchea performed the first PIPAC procedure in the United States in December 2019.
 

Innovative therapies needed

Peritoneal carcinomatosis is often a late-stage manifestation of abdominal cancers and is usually lethal, Dr. Dellinger said. She noted that systemic chemotherapy in the palliative setting is relatively ineffective in patients with peritoneal carcinomatosis because of pharmacokinetic limitations, poor peritoneal drug uptake, and impaired local drug distribution.

“Innovative, effective therapies are urgently needed for people who have ovarian, uterine, gastric, or colorectal cancer with peritoneal carcinomatosis,” Dr. Dellinger said.

“PIPAC is a novel treatment option that has had very favorable and exciting results,” Dr. Merchea said. “It is a potential option for patients when no other treatment options exist, and it is an avenue to provide hope to patients when often they have none.”

Potential candidates for PIPAC include patients who have peritoneal carcinomatosis, have failed other standard therapies, have more than 6 months’ life expectancy, and are not candidates for cytoreduction with HIPEC. There remains very limited data on the use of PIPAC as a neoadjuvant approach to convert patients who were previously unresectable to resectable disease, Dr. Merchea noted.

“To deliver chemotherapy directly to the tumor under pressure allows PIPAC to better penetrate the peritoneal surface and tumor nodules than traditional approaches, such as HIPEC,” Dr. Merchea said. “And the drug distribution at the tissue level is better than what is often achieved by systemic chemotherapy, but without the systemic effects of chemotherapy, such as hair loss. The treatment gives essentially a real-time, quantitative assessment of response by being able to directly assess the tumor via laparoscopic visualization and repeat biopsy.”

“Importantly, patients who undergo PIPAC don’t notice a decrease in their quality of life, and some patients note improvement, particularly with respect to nausea, vomiting, appetite, fatigue, and constipation,” Dr. Merchea said.
 

Trial details

The phase 1 trial of PIPAC will include a maximum of 24 patients. They will receive treatment every 6 weeks for up to three cycles and be followed for up to 3 years.

Patients with ovarian, uterine, or gastric cancer will undergo PIPAC with cisplatin, followed by doxorubicin. Patients with colorectal cancer will undergo PIPAC with oxaliplatin preceded by leucovorin and fluorouracil for cycles 2 and 3.

The researchers also plan to profile patients’ tumors.

“Tumor samples will be chronologically evaluated with genomics, spatial transcriptomics, pharmacodynamics, and single-cell sequencing throughout a patient’s treatment course, thus elucidating the treatment effects and natural history of peritoneal cancers,” Dr. Dellinger said.

The trial sites include City of Hope, Mayo Clinic in Florida, Northwell Health in New York, and the National Cancer Institute in Maryland.

The trial is sponsored by City of Hope in collaboration with the National Cancer Institute. Dr. Merchea and Dr. Dellinger reported having no conflicts of interest.

A team of U.S. researchers is investigating whether pressurized intraperitoneal aerosolized chemotherapy (PIPAC) can benefit patients with advanced cancer and peritoneal carcinomatosis.

City of Hope

The team’s phase 1 trial is the first in the United States to test PIPAC, and it will enroll patients with ovarian, uterine, colorectal, or gastric cancer who have peritoneal carcinomatosis.

Data from studies outside the United States suggest PIPAC can induce regression of peritoneal carcinomatosis, even in end-stage, therapy-resistant gastric, ovarian, and colorectal cancers (Lancet Oncol. 2019 Jul;20[7]:e368-e377).

The current study (NCT04329494) formally introduces PIPAC to the United States and serves as a launching pad for further investigation into how the treatment should be administered and which types of chemotherapies can be used.
 

About PIPAC

“PIPAC is a novel therapeutic approach that is minimally invasive, does not require cytoreduction, and can be repeated frequently,” said Thanh Dellinger, MD, a gynecologic oncology surgeon at City of Hope in Duarte, Calif., and co–principal investigator of the phase 1 trial.

“[PIPAC] entails accessing the abdominal cavity using standard laparoscopic techniques and relies on the increased intra-abdominal pressure (15 mm Hg) achieved with laparoscopic surgery, which generates a convective flux that forces aerosolized chemotherapy drugs from the peritoneal cavity into the subperitoneal tissue and overcomes the tumor’s interstitial pressure,” Dr. Dellinger explained in an interview.

“The surgical procedure to deliver PIPAC does not typically cause adhesive disease and allows for repeated delivery of intraperitoneal chemotherapy, objective tumor staging, and response assessment,” she noted.

Dr. Dellinger said the advantages of PIPAC include a minimally invasive approach; no debulking surgery required; deeper uptake of drugs in tumor tissues; wider, more effective drug distribution; fewer toxicities caused by lower drug dosage; repeatable administration; and palliation of peritoneal carcinomatosis symptoms, including abdominal bloating and ascites.

PIPAC achieves a deeper peritoneal nodule penetration of several millimeters with cisplatin, compared to less than 1 mm with heated intraoperative peritoneal chemotherapy (HIPEC) and other intraperitoneal methods, according to Amit Merchea, MD, an assistant professor of surgery at the Mayo Clinic in Jacksonville, Fla.

Dr. Merchea performed the first PIPAC procedure in the United States in December 2019.
 

Innovative therapies needed

Peritoneal carcinomatosis is often a late-stage manifestation of abdominal cancers and is usually lethal, Dr. Dellinger said. She noted that systemic chemotherapy in the palliative setting is relatively ineffective in patients with peritoneal carcinomatosis because of pharmacokinetic limitations, poor peritoneal drug uptake, and impaired local drug distribution.

“Innovative, effective therapies are urgently needed for people who have ovarian, uterine, gastric, or colorectal cancer with peritoneal carcinomatosis,” Dr. Dellinger said.

“PIPAC is a novel treatment option that has had very favorable and exciting results,” Dr. Merchea said. “It is a potential option for patients when no other treatment options exist, and it is an avenue to provide hope to patients when often they have none.”

Potential candidates for PIPAC include patients who have peritoneal carcinomatosis, have failed other standard therapies, have more than 6 months’ life expectancy, and are not candidates for cytoreduction with HIPEC. There remains very limited data on the use of PIPAC as a neoadjuvant approach to convert patients who were previously unresectable to resectable disease, Dr. Merchea noted.

“To deliver chemotherapy directly to the tumor under pressure allows PIPAC to better penetrate the peritoneal surface and tumor nodules than traditional approaches, such as HIPEC,” Dr. Merchea said. “And the drug distribution at the tissue level is better than what is often achieved by systemic chemotherapy, but without the systemic effects of chemotherapy, such as hair loss. The treatment gives essentially a real-time, quantitative assessment of response by being able to directly assess the tumor via laparoscopic visualization and repeat biopsy.”

“Importantly, patients who undergo PIPAC don’t notice a decrease in their quality of life, and some patients note improvement, particularly with respect to nausea, vomiting, appetite, fatigue, and constipation,” Dr. Merchea said.
 

Trial details

The phase 1 trial of PIPAC will include a maximum of 24 patients. They will receive treatment every 6 weeks for up to three cycles and be followed for up to 3 years.

Patients with ovarian, uterine, or gastric cancer will undergo PIPAC with cisplatin, followed by doxorubicin. Patients with colorectal cancer will undergo PIPAC with oxaliplatin preceded by leucovorin and fluorouracil for cycles 2 and 3.

The researchers also plan to profile patients’ tumors.

“Tumor samples will be chronologically evaluated with genomics, spatial transcriptomics, pharmacodynamics, and single-cell sequencing throughout a patient’s treatment course, thus elucidating the treatment effects and natural history of peritoneal cancers,” Dr. Dellinger said.

The trial sites include City of Hope, Mayo Clinic in Florida, Northwell Health in New York, and the National Cancer Institute in Maryland.

The trial is sponsored by City of Hope in collaboration with the National Cancer Institute. Dr. Merchea and Dr. Dellinger reported having no conflicts of interest.