User login
Durable efficacy with MK-6482 in VHL-associated RCC
according to a presentation at the European Society for Medical Oncology Virtual Congress 2020.
MK-6482 is an oral inhibitor of hypoxia inducible factor-(HIF) 2-alpha. The drug previously showed favorable safety and antitumor activity in advanced RCC, Ramaprasad Srinivasan, MD, PhD, of the National Cancer Institute, Bethesda, Md., said when presenting data from the phase 2 trial.
Dr. Srinivasan noted that, in VHL disease, RCC occurs in 25%-60% of individuals and is a key cause of morbidity and shortened life expectancy despite aggressive treatment. HIF-2-alpha accumulation activates genes that drive tumor growth in VHL-associated RCC.
The primary objective of Dr. Srinivasan’s phase 2 study was to evaluate the efficacy of the HIF-2-alpha inhibitor MK-6482 (at 120 mg daily) for the treatment of VHL-associated RCC.
The study included 61 treatment-naive patients with VHL diagnoses based on germline mutations. All subjects had RCC and additional non-RCC lesions, including pancreatic (100%), central nervous system (CNS) hemangioblastoma (70.5%), and retinal lesions (26.2%).
The patients’ median age at baseline was 41 years (range, 19-66), and 52.5% were men. Most (82%) had an European Cooperative Oncology Group performance status of 0.
Efficacy and safety
At a median follow-up of 68.7 weeks, 56 patients were receiving ongoing treatment.
By independent central review, the overall response rate in target RCC lesions was 36.1% (all partial responses), with unconfirmed partial responses in 11.5% and stable disease in 62.3%. There was no progression in target lesions. Decreases in target lesion size were observed in 91.8% of patients.
The median time to response was 31.1 weeks (range, 11.9-62.3 weeks), and the median duration of response was not reached (range, 11.9-62.3 weeks). The 1-year progression-free survival rate was 98.3%.
“Promising clinical activity was observed with MK-6482 in treatment-naive patients with VHL-associated RCC,” Dr. Srinivasan said. He added that efficacy was durable in both RCC and non-renal lesions.
Complete responses were observed in 6.6% (4/61) of pancreatic lesions and 11.6% (5/43) of CNS hemangioblastomas. Partial response and stable disease rates in pancreatic lesions were 57.4% and 34.4%, respectively. Partial response and stable disease rates in CNS hemangioblastomas were 18.6% and 65.1%, respectively.
In the 16 patients with retinal lesions, 68.8% saw an improvement and 25% had stable disease. No progression was reported.
“MK-6482 was well tolerated and has a favorable safety profile,” Dr. Srinivasan noted.
Most patients (98.4%) had treatment-related adverse events (AEs), with anemia being the most common. Grade 3 AEs included anemia (6.6%), fatigue (4.9%), dyspnea (1.6%), and hypoxia (1.6%). One patient (1.6%) discontinued treatment because of grade 1 dizziness. There was one grade 4 AE and one fatal AE, but both were considered unrelated to study treatment.
Remaining questions and next steps
The challenge in managing VHL-associated RCC tumors is finding a balance between the risk of cancer dissemination and renal morbidity, said study discussant Cristina Suárez, MD, PhD, of Hospital Universitari Vall d’Hebron in Barcelona.
“There is no standard of care systemic treatment, and recruitment for clinical trials is challenging,” Dr. Suárez added.
While response rates in RCC lesions with MK-6482 were generally in line with the experience reported for sunitinib and pazopanib, response rates were particularly favorable with MK-6482 in pancreatic lesions and CNS hemangioblastomas, Dr. Suárez said.
“These are the best response rates reported in non-RCC lesions,” she noted.
However, Dr. Suárez said, important questions remain. Specifically, how long should patients continue on treatment, and will lesion rebound occur after treatment discontinuation?
Larger multicenter trials are needed, Dr. Suárez said, pointing out that the current study is the largest to date of systemic therapy for patients with VHL disease.
The study was funded by Merck Sharp & Dohme Corp. Dr. Srinivasan disclosed funding from Merck and Calithera Biosciences. Dr. Suárez disclosed relationships with Astellas, AstraZeneca, Bayer, and many other companies.
SOURCE: Srinivasan R et al. ESMO 2020. Abstract LBA26.
according to a presentation at the European Society for Medical Oncology Virtual Congress 2020.
MK-6482 is an oral inhibitor of hypoxia inducible factor-(HIF) 2-alpha. The drug previously showed favorable safety and antitumor activity in advanced RCC, Ramaprasad Srinivasan, MD, PhD, of the National Cancer Institute, Bethesda, Md., said when presenting data from the phase 2 trial.
Dr. Srinivasan noted that, in VHL disease, RCC occurs in 25%-60% of individuals and is a key cause of morbidity and shortened life expectancy despite aggressive treatment. HIF-2-alpha accumulation activates genes that drive tumor growth in VHL-associated RCC.
The primary objective of Dr. Srinivasan’s phase 2 study was to evaluate the efficacy of the HIF-2-alpha inhibitor MK-6482 (at 120 mg daily) for the treatment of VHL-associated RCC.
The study included 61 treatment-naive patients with VHL diagnoses based on germline mutations. All subjects had RCC and additional non-RCC lesions, including pancreatic (100%), central nervous system (CNS) hemangioblastoma (70.5%), and retinal lesions (26.2%).
The patients’ median age at baseline was 41 years (range, 19-66), and 52.5% were men. Most (82%) had an European Cooperative Oncology Group performance status of 0.
Efficacy and safety
At a median follow-up of 68.7 weeks, 56 patients were receiving ongoing treatment.
By independent central review, the overall response rate in target RCC lesions was 36.1% (all partial responses), with unconfirmed partial responses in 11.5% and stable disease in 62.3%. There was no progression in target lesions. Decreases in target lesion size were observed in 91.8% of patients.
The median time to response was 31.1 weeks (range, 11.9-62.3 weeks), and the median duration of response was not reached (range, 11.9-62.3 weeks). The 1-year progression-free survival rate was 98.3%.
“Promising clinical activity was observed with MK-6482 in treatment-naive patients with VHL-associated RCC,” Dr. Srinivasan said. He added that efficacy was durable in both RCC and non-renal lesions.
Complete responses were observed in 6.6% (4/61) of pancreatic lesions and 11.6% (5/43) of CNS hemangioblastomas. Partial response and stable disease rates in pancreatic lesions were 57.4% and 34.4%, respectively. Partial response and stable disease rates in CNS hemangioblastomas were 18.6% and 65.1%, respectively.
In the 16 patients with retinal lesions, 68.8% saw an improvement and 25% had stable disease. No progression was reported.
“MK-6482 was well tolerated and has a favorable safety profile,” Dr. Srinivasan noted.
Most patients (98.4%) had treatment-related adverse events (AEs), with anemia being the most common. Grade 3 AEs included anemia (6.6%), fatigue (4.9%), dyspnea (1.6%), and hypoxia (1.6%). One patient (1.6%) discontinued treatment because of grade 1 dizziness. There was one grade 4 AE and one fatal AE, but both were considered unrelated to study treatment.
Remaining questions and next steps
The challenge in managing VHL-associated RCC tumors is finding a balance between the risk of cancer dissemination and renal morbidity, said study discussant Cristina Suárez, MD, PhD, of Hospital Universitari Vall d’Hebron in Barcelona.
“There is no standard of care systemic treatment, and recruitment for clinical trials is challenging,” Dr. Suárez added.
While response rates in RCC lesions with MK-6482 were generally in line with the experience reported for sunitinib and pazopanib, response rates were particularly favorable with MK-6482 in pancreatic lesions and CNS hemangioblastomas, Dr. Suárez said.
“These are the best response rates reported in non-RCC lesions,” she noted.
However, Dr. Suárez said, important questions remain. Specifically, how long should patients continue on treatment, and will lesion rebound occur after treatment discontinuation?
Larger multicenter trials are needed, Dr. Suárez said, pointing out that the current study is the largest to date of systemic therapy for patients with VHL disease.
The study was funded by Merck Sharp & Dohme Corp. Dr. Srinivasan disclosed funding from Merck and Calithera Biosciences. Dr. Suárez disclosed relationships with Astellas, AstraZeneca, Bayer, and many other companies.
SOURCE: Srinivasan R et al. ESMO 2020. Abstract LBA26.
according to a presentation at the European Society for Medical Oncology Virtual Congress 2020.
MK-6482 is an oral inhibitor of hypoxia inducible factor-(HIF) 2-alpha. The drug previously showed favorable safety and antitumor activity in advanced RCC, Ramaprasad Srinivasan, MD, PhD, of the National Cancer Institute, Bethesda, Md., said when presenting data from the phase 2 trial.
Dr. Srinivasan noted that, in VHL disease, RCC occurs in 25%-60% of individuals and is a key cause of morbidity and shortened life expectancy despite aggressive treatment. HIF-2-alpha accumulation activates genes that drive tumor growth in VHL-associated RCC.
The primary objective of Dr. Srinivasan’s phase 2 study was to evaluate the efficacy of the HIF-2-alpha inhibitor MK-6482 (at 120 mg daily) for the treatment of VHL-associated RCC.
The study included 61 treatment-naive patients with VHL diagnoses based on germline mutations. All subjects had RCC and additional non-RCC lesions, including pancreatic (100%), central nervous system (CNS) hemangioblastoma (70.5%), and retinal lesions (26.2%).
The patients’ median age at baseline was 41 years (range, 19-66), and 52.5% were men. Most (82%) had an European Cooperative Oncology Group performance status of 0.
Efficacy and safety
At a median follow-up of 68.7 weeks, 56 patients were receiving ongoing treatment.
By independent central review, the overall response rate in target RCC lesions was 36.1% (all partial responses), with unconfirmed partial responses in 11.5% and stable disease in 62.3%. There was no progression in target lesions. Decreases in target lesion size were observed in 91.8% of patients.
The median time to response was 31.1 weeks (range, 11.9-62.3 weeks), and the median duration of response was not reached (range, 11.9-62.3 weeks). The 1-year progression-free survival rate was 98.3%.
“Promising clinical activity was observed with MK-6482 in treatment-naive patients with VHL-associated RCC,” Dr. Srinivasan said. He added that efficacy was durable in both RCC and non-renal lesions.
Complete responses were observed in 6.6% (4/61) of pancreatic lesions and 11.6% (5/43) of CNS hemangioblastomas. Partial response and stable disease rates in pancreatic lesions were 57.4% and 34.4%, respectively. Partial response and stable disease rates in CNS hemangioblastomas were 18.6% and 65.1%, respectively.
In the 16 patients with retinal lesions, 68.8% saw an improvement and 25% had stable disease. No progression was reported.
“MK-6482 was well tolerated and has a favorable safety profile,” Dr. Srinivasan noted.
Most patients (98.4%) had treatment-related adverse events (AEs), with anemia being the most common. Grade 3 AEs included anemia (6.6%), fatigue (4.9%), dyspnea (1.6%), and hypoxia (1.6%). One patient (1.6%) discontinued treatment because of grade 1 dizziness. There was one grade 4 AE and one fatal AE, but both were considered unrelated to study treatment.
Remaining questions and next steps
The challenge in managing VHL-associated RCC tumors is finding a balance between the risk of cancer dissemination and renal morbidity, said study discussant Cristina Suárez, MD, PhD, of Hospital Universitari Vall d’Hebron in Barcelona.
“There is no standard of care systemic treatment, and recruitment for clinical trials is challenging,” Dr. Suárez added.
While response rates in RCC lesions with MK-6482 were generally in line with the experience reported for sunitinib and pazopanib, response rates were particularly favorable with MK-6482 in pancreatic lesions and CNS hemangioblastomas, Dr. Suárez said.
“These are the best response rates reported in non-RCC lesions,” she noted.
However, Dr. Suárez said, important questions remain. Specifically, how long should patients continue on treatment, and will lesion rebound occur after treatment discontinuation?
Larger multicenter trials are needed, Dr. Suárez said, pointing out that the current study is the largest to date of systemic therapy for patients with VHL disease.
The study was funded by Merck Sharp & Dohme Corp. Dr. Srinivasan disclosed funding from Merck and Calithera Biosciences. Dr. Suárez disclosed relationships with Astellas, AstraZeneca, Bayer, and many other companies.
SOURCE: Srinivasan R et al. ESMO 2020. Abstract LBA26.
ESMO 2020
Clinical factors and treatment tied to COVID-19 mortality in cancer patients
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
according to two presentations at the European Society for Medical Oncology Virtual Congress 2020.
Two analyses of data from the COVID-19 and Cancer Consortium (CCC19) were presented at the meeting.
The data suggest that older age, male sex, more comorbidities, poor performance status, progressive cancer or multiple cancers, hematologic malignancy, and recent cancer therapy are all associated with higher mortality among patients with cancer and COVID-19. Anti-CD20 therapy is associated with an especially high mortality rate, according to an investigator.
Among hospitalized patients, increased absolute neutrophil count as well as abnormal D-dimer, high-sensitivity troponin, and C-reactive protein are associated with a higher risk of mortality.
Prior analyses of CCC19 data pointed to several factors associated with higher COVID-19 death rates, according to Petros Grivas, MD, PhD, of University of Washington, Seattle, who presented some CCC19 data at the meeting. However, the prior analyses were limited by weak statistical power and low event rates, Dr. Grivas said.
Clinical and laboratory factors: Abstract LBA72
The aim of Dr. Grivas’s analysis was to validate a priori identified demographic and clinicopathologic factors associated with 30-day all-cause mortality in patients with COVID-19 and cancer. Dr. Grivas and colleagues also explored the potential association between laboratory parameters and 30-day all-cause mortality.
The analysis included 3,899 patients with cancer and COVID-19 from 124 centers. Most centers are in the United States, but 4% are in Canada, and 2% are in Spain. About two-thirds of patients were 60 years of age or younger at baseline, half were men, 79% had solid tumors, and 21% had hematologic malignancies.
Cancer-specific factors associated with an increased risk of 30-day all-cause mortality were having progressive cancer (adjusted odds ratio, 2.9), receiving cancer therapy within 3 months (aOR, 1.2), having a hematologic versus solid tumor (aOR, 1.7), and having multiple malignancies (aOR, 1.5).
Clinical factors associated with an increased risk of 30-day all-cause mortality were Black versus White race (aOR, 1.5), older age (aOR, 1.7 per 10 years), three or more actively treated comorbidities (versus none; aOR, 2.1), and Eastern Cooperative Oncology Group performance status of 2 or more (versus 0; aOR, 4.6).
In hospitalized patients, several laboratory variables were associated with an increased risk of 30-day all-cause mortality. Having an absolute neutrophil count above the upper limit of normal doubled the risk (aOR, 2.0), while abnormal D-dimer, high-sensitivity troponin, and C-reactive protein all more than doubled the risk of mortality (aORs of 2.5, 2.5, and 2.4, respectively).
Further risk modeling with multivariable analysis will be performed after longer follow-up, Dr. Grivas noted.
Treatment-related outcomes: Abstract LBA71
An additional analysis of CCC19 data encompassed 3,654 patients. In this analysis, researchers investigated the correlation between timing of cancer treatment and COVID-19–related complications and 30-day mortality.
Mortality was highest among cancer patients treated 1-3 months prior to COVID-19 diagnosis, with all-cause mortality at 28%, said Trisha M. Wise-Draper, MD, PhD, of University of Cincinnati, when presenting the data at the meeting.
Rates for other complications (hospitalization, oxygen required, ICU admission, and mechanical ventilation) were similar regardless of treatment timing.
The unadjusted 30-day mortality rate was highest for patients treated most recently with chemoimmunotherapy (30%), followed by chemotherapy (18%), chemoradiotherapy (18%), and targeted therapy (17%).
The mortality rate was “particularly high,” at 50%, in patients receiving anti-CD20 therapy 1-3 months prior to COVID-19 diagnosis – the time period for which significant B-cell depletion develops, Dr. Wise-Draper observed.
An analysis of disease status among 1,449 patients treated within 3 months of COVID-19 diagnosis showed mortality risk increasing from 6% among patients in remission or with newly emergent disease, to 22% in patients with any active cancer, to 34% in those with progressing disease, Dr. Wise-Draper said.
Discussant Benjamin Solomon, MD, PhD, of Peter MacCallum Cancer Centre in Melbourne, made note of the high 30-day mortality rate seen in patients receiving anti-CD20 therapy as well as the elevated standardized mortality ratios with recent chemoimmunotherapy and targeted therapy.
“Although there are some limitations of this analysis, it provides the best data we have to date about the effects of treatment on early mortality in patients with COVID-19 and cancer. It points to a modest but heterogeneous effect of treatment on outcome, one which is likely to become clearer with larger cohorts and additional analysis,” Dr. Solomon said.
This research was funded by the American Cancer Society, Hope Foundation for Cancer Research, Jim and Carol O’Hare Fund, National Cancer Institute, National Human Genome Research Institute, Vanderbilt Institute for Clinical and Translational Research, and Fonds de Recherche du Quebec-Sante. Dr. Grivas disclosed relationships with many companies, but none are related to this work. Dr. Wise-Draper disclosed relationships with Merck, Bristol-Myers Squibb, Tesaro, GlaxoSmithKline, AstraZeneca, Shattuck Labs, and Rakuten. Dr. Solomon disclosed relationships with Amgen, AstraZeneca, Merck, Bristol-Myers Squibb, Novartis, Pfizer, and Roche-Genentech.
SOURCES: Grivas P et al. ESMO 2020, Abstract LBA72; Wise-Draper TM et al. ESMO 2020, Abstract LBA71.
FROM ESMO 2020
The scope of under- and overtreatment in older adults with cancer
Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.
Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.
Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.
The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
About scoping reviews
Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.
Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:
- Establish eligibility criteria with a rationale for each criterion clearly explained
- Search multiple databases in multiple languages
- Include “gray literature,” defined as studies that are unpublished or difficult to locate
- Have several independent reviewers screen titles and abstracts
- Ask multiple independent reviewers to review full text articles
- Present results with charts or diagrams that align with the review’s objective
- Graphically depict the decision process for including/excluding sources
- Identify implications for further research.
In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.
Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
Findings and implications
To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.
For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.
Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).
Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).
Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
Care of individual patients and clinical research
National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.
In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.
Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.
The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.
Employing disease-centric and geriatric domains
Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.
Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.
As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.
An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).
Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.
Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.
These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.
Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.
Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.
Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.
The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
About scoping reviews
Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.
Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:
- Establish eligibility criteria with a rationale for each criterion clearly explained
- Search multiple databases in multiple languages
- Include “gray literature,” defined as studies that are unpublished or difficult to locate
- Have several independent reviewers screen titles and abstracts
- Ask multiple independent reviewers to review full text articles
- Present results with charts or diagrams that align with the review’s objective
- Graphically depict the decision process for including/excluding sources
- Identify implications for further research.
In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.
Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
Findings and implications
To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.
For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.
Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).
Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).
Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
Care of individual patients and clinical research
National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.
In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.
Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.
The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.
Employing disease-centric and geriatric domains
Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.
Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.
As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.
An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).
Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.
Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.
These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.
Because of physiological changes with aging and differences in cancer biology, caring for older adults (OAs) with cancer requires careful assessment and planning.
Clark Dumontier, MD, of Brigham and Women’s Hospital in Boston, and colleagues sought to define the meaning of the terms “undertreatment” and “overtreatment” for OAs with cancer in a scoping literature review published in the Journal of Clinical Oncology.
Though OAs are typically defined as adults aged 65 years and older, in this review, the authors defined OAs as patients aged 60 years and older.
The authors theorized that a scoping review of papers about this patient population could provide clues about limitations in the oncology literature and guidance about patient management and future research. Despite comprising the majority of cancer patients, OAs are underrepresented in clinical trials.
About scoping reviews
Scoping reviews are used to identify existing evidence in a field, clarify concepts or definitions in the literature, survey how research on a topic is conducted, and identify knowledge gaps. In addition, scoping reviews summarize available evidence without answering a discrete research question.
Industry standards for scoping reviews have been established by the Johanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. According to these standards, scoping reviews should:
- Establish eligibility criteria with a rationale for each criterion clearly explained
- Search multiple databases in multiple languages
- Include “gray literature,” defined as studies that are unpublished or difficult to locate
- Have several independent reviewers screen titles and abstracts
- Ask multiple independent reviewers to review full text articles
- Present results with charts or diagrams that align with the review’s objective
- Graphically depict the decision process for including/excluding sources
- Identify implications for further research.
In their review, Dr. DuMontier and colleagues fulfilled many of the aforementioned criteria. The team searched three English-language databases for titles and abstracts that included the terms undertreatment and/or overtreatment, and were related to OAs with cancer, inclusive of all types of articles, cancer types, and treatments.
Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived. Within a random subset of articles, two coauthors independently determined final categories of definitions and independently assigned those categories.
Findings and implications
To define OA, Dr. DuMontier and colleagues used a cutoff of 60 years or older. Articles mentioning undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion (n = 256), but only 14 articles (5.5%) explicitly provided formal definitions.
For most of the reviewed articles, the authors judged definitions from the surrounding context. In a random subset of 50 articles, there was a high level of agreement (87.1%; κ = 0.81) between two coauthors in independently assigning categories of definitions.
Undertreatment was applied to therapy that was less than recommended (148 articles; 62.7%) or less than recommended with worse outcomes (88 articles; 37.3%).
Overtreatment most commonly denoted intensive treatment of an OA in whom harms outweighed the benefits of treatment (38 articles; 53.5%) or intensive treatment of a cancer not expected to affect the OA during the patient’s remaining life (33 articles; 46.5%).
Overall, the authors found that undertreatment and overtreatment of OAs with cancer are imprecisely defined concepts. Formal geriatric assessment was recommended in just over half of articles, and only 26.2% recommended formal assessments of age-related vulnerabilities for management. The authors proposed definitions that accounted for both oncologic factors and geriatric domains.
Care of individual patients and clinical research
National Comprehensive Cancer Network (NCCN) guidelines for OAs with cancer recommend initial consideration of overall life expectancy. If a patient is a candidate for cancer treatment on that basis, the next recommended assessment is that of the patient’s capacity to understand the relevant information, appreciate the underlying values and overall medical situation, reason through decisions, and communicate a choice that is consistent with the patient’s articulated goals.
In the pretreatment evaluation of OAs in whom there are no concerns about tolerance to antineoplastic therapy, NCCN guidelines suggest geriatric screening with standardized tools and, if abnormal, comprehensive geriatric screening. The guidelines recommend considering alternative treatment options if nonmodifiable abnormalities are identified.
Referral to a geriatric clinical specialist, use of the Cancer and Aging Research Group’s Chemo Toxicity Calculator, and calculation of Chemotherapy Risk Assessment Scale for High-Age Patients score are specifically suggested if high-risk procedures (such as chemotherapy, radiation, or complex surgery, which most oncologists would consider to be “another day in the office”) are contemplated.
The American Society of Clinical Oncology (ASCO) guidelines for geriatric oncology are similarly detailed and endorse similar evaluations and management.
Employing disease-centric and geriatric domains
Dr. DuMontier and colleagues noted that, for OAs with comorbidity or psychosocial challenges, surrogate survival endpoints are unrelated to quality of life (QOL) outcomes. Nonetheless, QOL is valued by OAs at least as much as survival improvement.
Through no fault of their own, the authors’ conclusion that undertreatment and overtreatment are imperfectly defined concepts has a certain neutrality to it. However, the terms undertreatment and overtreatment are commonly used to signify that inappropriate treatment decisions were made. Therefore, the terms are inherently negative and pejorative.
As with most emotionally charged issues in oncology, it is ideal for professionals in our field to take charge when deficiencies exist. ASCO, NCCN, and the authors of this scoping review have provided a conceptual basis for doing so.
An integrated oncologist-geriatrician approach was shown to be effective in the randomized INTEGERATE trial, showing improved QOL, reduced hospital admissions, and reduced early treatment discontinuation from adverse events (ASCO 2020, Abstract 12011).
Therefore, those clinicians who have not formally, systematically, and routinely supplemented the traditional disease-centric endpoints with patient-centered criteria need to do so.
Similarly, a retrospective study published in JAMA Network Open demonstrated that geriatric and surgical comanagement of OAs with cancer was associated with significantly lower 90-day postoperative mortality and receipt of more supportive care services (physical therapy, occupational therapy, speech and swallow rehabilitation, and nutrition services), in comparison with management from the surgical service only.
These clinical and administrative changes will not only enhance patient management but also facilitate the clinical trials required to clarify optimal treatment intensity. As that occurs, we will be able to apply as much precision to the care of OAs with cancer as we do in other areas of cancer treatment.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Dumontier C et al. J Clin Oncol. 2020 Aug 1;38(22):2558-2569.
Cancer disparities: One of the most pressing public health issues
“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.”
AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.
He noted that:
- Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
- Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
- Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
- Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
- In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.
“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
Making progress against cancer
Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.
U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.
Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.
A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.
This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.
However, both reports agree that more must be done to reduce cancer disparities even further.
They highlight initiatives that are underway, including:
- The draft guidance issued by the FDA to promote diversification of clinical trial populations.
- The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
- The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
- The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.
Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.
Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.
Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.
“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.
Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.
The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”
Ribas further called for action from national leadership and the scientific community.
“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”
This article first appeared on Medscape.com.
“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.”
AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.
He noted that:
- Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
- Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
- Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
- Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
- In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.
“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
Making progress against cancer
Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.
U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.
Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.
A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.
This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.
However, both reports agree that more must be done to reduce cancer disparities even further.
They highlight initiatives that are underway, including:
- The draft guidance issued by the FDA to promote diversification of clinical trial populations.
- The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
- The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
- The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.
Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.
Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.
Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.
“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.
Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.
The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”
Ribas further called for action from national leadership and the scientific community.
“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”
This article first appeared on Medscape.com.
“The burden of cancer is not shouldered equally by all segments of the U.S. population,” the AACR adds. “The adverse differences in cancer burden that exist among certain population groups are one of the most pressing public health challenges that we face in the United States.”
AACR president Antoni Ribas, MD, PhD, gave some examples of these disparities at a September 16 Congressional briefing that focused on the inaugural AACR Cancer Disparities Progress Report 2020.
He noted that:
- Black men have more than double the rate of death from prostate cancer compared with men of other racial and ethnic groups.
- Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.
- Non-Hispanic Black children and adolescents with cancer are more than 50% more likely to die from the cancer than non-Hispanic white children and adolescents with cancer.
- Women of low socioeconomic status with early stage ovarian cancer are 50% less likely to receive recommended care than are women of high socioeconomic status.
- In addition to racial and ethnic minority groups, other populations that bear a disproportionate burden when it comes to cancer include individuals lacking adequate health insurance coverage, immigrants, those with disabilities, residents in rural areas, and members of the lesbian, gay, bisexual, and transgender communities.
“It is absolutely unacceptable that advances in cancer care and treatment are not benefiting everyone equally,” Ribas commented.
Making progress against cancer
Progress being made against cancer was highlighted in another publication, the annual AACR Cancer Progress Report 2020.
U.S. cancer deaths declined by 29% between 1991 and 2017, translating to nearly 3 million cancer deaths avoided, the report notes. In addition, 5-year survival rates for all cancers combined increased from 49% in the mid-1970s to 70% for patients diagnosed from 2010-2016.
Between August 2019 and July 31 of this year, the U.S. Food and Drug Administration approved 20 new anticancer drugs for various cancer types and 15 new indications for previously approved cancer drugs, marking the highest number of approvals in one 12-month period since AACR started producing these reports 10 years ago.
A continuing reduction in the cigarette smoking rate among US adults, which is now below 14%, is contributing greatly to declines in lung cancer rates, which have largely driven the improvements in cancer survival, the AACR noted.
This report also notes that progress has been made toward reducing cancer disparities. Overall disparities in cancer death rates among racial and ethnic groups are less pronounced now than they have been in the past two decades. For example, the overall cancer death rate for African American patients was 33% higher than for White patients in 1990 but just 14% higher in 2016.
However, both reports agree that more must be done to reduce cancer disparities even further.
They highlight initiatives that are underway, including:
- The draft guidance issued by the FDA to promote diversification of clinical trial populations.
- The National Institutes of Health’s (NIH’s) Continuing Umbrella of Research Experiences (CURE) program supporting underrepresented students and scientists along their academic and research career pathway.
- The Centers for Disease Control and Prevention’s Racial and Ethnic Approaches to Community Health (REACH) program, a grant-making program focused on encouraging preventive behaviors in underserved communities.
- The NIH’s All of Us program, which is gathering information from the genomes of 1 million healthy individuals with a focus on recruitment from historically underrepresented populations.
Ribas also announced that AACR has established a task force to focus on racial inequalities in cancer research.
Eliminating disparities would save money, argued John D. Carpten, PhD, from the University of Southern California, Los Angeles, who chaired the steering committee that developed the AACR Cancer Disparities Progress Report.
Carpten noted research showing that eliminating disparities for racial and ethnic minorities between 2003 and 2006 would have reduced health care costs by more than $1 trillion in the United States. This underscores the potentially far-reaching impact of efforts to eliminate disparities, he said.
“Without a doubt, socioeconomics and inequities in access to quality care represent major factors influencing cancer health disparities, and these disparities will persist until we address these issues” he said.
Both progress reports culminate in a call to action, largely focused on the need for “unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for the NIH, NCI [National Cancer Institute], and FDA,” which is vital for accelerating the pace of progress.
The challenge is now compounded by the ongoing COVID-19 pandemic: Both progress reports note that racial and ethnic minorities, including African Americans, are not only affected disproportionately by cancer, but also by COVID-19, further highlighting the “stark inequities in health care.”
Ribas further called for action from national leadership and the scientific community.
“During this unprecedented time in our nation’s history, there is also a need for our nation’s leaders to take on a much bigger role in confronting and combating the structural and systemic racism that contributes to health disparities,” he said. The “pervasive racism and social injustices” that have contributed to disparities in both COVID-19 and cancer underscore the need for “the scientific community to step up and partner with Congress to assess and address this issue within the research community.”
This article first appeared on Medscape.com.
Predicting complications of cytoreductive nephrectomy in metastatic RCC
according to an analysis of registry data.
Higher intraoperative blood loss was also associated with low-grade postoperative complications. Intraoperative complications were more likely in patients who had concurrent thrombectomy and surgery on adjacent organs.
Eduard Roussel, MD, of University Hospitals Leuven (Belgium) and colleagues reported these findings in European Urology Oncology.
The authors noted that the role of CN in metastatic RCC is controversial. The CARMENA trial, published in the New England Journal of Medicine, “shifted treatment paradigms” away from surgery by suggesting that sunitinib alone is noninferior to sunitinib after CN.
“Nonetheless, there is a general consensus that certain selected subgroups of patients with low-volume, single-site metastases and few adverse IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria would still benefit from the continued use of upfront CN,” the authors wrote.
They advised clinicians to weigh the risks and benefits of CN, particularly because “postoperative morbidity might preclude or delay the use of subsequent systemic therapies.” However, the risk/benefit calculation for CN has been difficult because past investigations have tended to focus only on survival outcomes, so there isn’t much data on morbidity, the authors wrote.
Patient characteristics and complications
To investigate morbidity associated with CN, Dr. Roussel and colleagues reviewed data from the Registry of Metastatic RCC (REMARCC). The team analyzed the clinical records of 736 patients who underwent nephrectomy for metastatic RCC during 1980-2019.
The patients’ median age was 63 years (range, 55-70 years), and about three-quarters were men. The majority had clear cell carcinoma, and the lungs were the most common site of metastases.
More than 97% of procedures were complete nephrectomies, and the rest were partial. The median estimated blood loss was 400 mL, and the median follow-up was 16.5 months.
There were 69 patients who had intraoperative complications, most commonly bleeding (n = 25), spleen laceration (n = 13), and vascular injury (n = 11).
There were 217 patients who had postoperative complications, including 45 patients with high-grade complications (grade 3-5) and 10 who died.
The most common postoperative complications were vascular/lymphatic in nature. These occurred in 67 patients and included 10 lymphoceles.
“[G]iven the relatively high rate of postoperative lymphoceles, which is probably attributable to the performance of lymph node dissections and the lack of proven oncological survival benefit thereof, surgeons might reconsider the performance of lymphadenectomy during CN,” the investigators wrote.
Other common postoperative complications included infectious and cardiopulmonary issues, which occurred in 42 and 39 patients, respectively.
Predictors of complications
Thrombectomy and adjacent organ removal were significant predictors of intraoperative complications on multivariable analysis. The odds ratios were 1.38 (P = .009) for thrombectomy and 2.71 (P = .004) for adjacent organ removal.
Estimated blood loss was a significant predictor of low- and high-grade postoperative complications. The OR for high-grade complications per 200 mL of blood lost was 1.06 (P = .007), and the OR for low-grade complications per 200 mL blood lost was 1.09 (P = .001).
There was a strong inverse correlation with CN case load at each center and high-grade postoperative complications, which highlights “the impact of centralization of care on postoperative outcomes in complex surgical scenarios,” the investigators wrote. The OR per 25 cases was 0.88 (P = .04).
Results were largely the same when the analysis was limited to the 560 subjects treated since 2006, in the targeted therapy era, except that adjacent organ removal as a predictor of intraoperative complications did not quite reach statistical significance (P = .06).
The presurgery risk factors identified in this study should assist with presurgical counseling, said Zachery Reichert, MD, PhD, a genitourinary medical oncologist and assistant professor at the University of Michigan, Ann Arbor, who was not involved in this study.
“This is especially important for patients who require thrombectomy or adjacent organ removal or do not have access to a surgeon with high cytoreductive nephrectomy caseloads,” he said.
Dr. Reichert reported having no disclosures. There was no external funding for this study, and the investigators didn’t have any disclosures.
SOURCE: Roussel E et al. Eur Urol Oncol. 2020 Aug;3(4):523-9.
according to an analysis of registry data.
Higher intraoperative blood loss was also associated with low-grade postoperative complications. Intraoperative complications were more likely in patients who had concurrent thrombectomy and surgery on adjacent organs.
Eduard Roussel, MD, of University Hospitals Leuven (Belgium) and colleagues reported these findings in European Urology Oncology.
The authors noted that the role of CN in metastatic RCC is controversial. The CARMENA trial, published in the New England Journal of Medicine, “shifted treatment paradigms” away from surgery by suggesting that sunitinib alone is noninferior to sunitinib after CN.
“Nonetheless, there is a general consensus that certain selected subgroups of patients with low-volume, single-site metastases and few adverse IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria would still benefit from the continued use of upfront CN,” the authors wrote.
They advised clinicians to weigh the risks and benefits of CN, particularly because “postoperative morbidity might preclude or delay the use of subsequent systemic therapies.” However, the risk/benefit calculation for CN has been difficult because past investigations have tended to focus only on survival outcomes, so there isn’t much data on morbidity, the authors wrote.
Patient characteristics and complications
To investigate morbidity associated with CN, Dr. Roussel and colleagues reviewed data from the Registry of Metastatic RCC (REMARCC). The team analyzed the clinical records of 736 patients who underwent nephrectomy for metastatic RCC during 1980-2019.
The patients’ median age was 63 years (range, 55-70 years), and about three-quarters were men. The majority had clear cell carcinoma, and the lungs were the most common site of metastases.
More than 97% of procedures were complete nephrectomies, and the rest were partial. The median estimated blood loss was 400 mL, and the median follow-up was 16.5 months.
There were 69 patients who had intraoperative complications, most commonly bleeding (n = 25), spleen laceration (n = 13), and vascular injury (n = 11).
There were 217 patients who had postoperative complications, including 45 patients with high-grade complications (grade 3-5) and 10 who died.
The most common postoperative complications were vascular/lymphatic in nature. These occurred in 67 patients and included 10 lymphoceles.
“[G]iven the relatively high rate of postoperative lymphoceles, which is probably attributable to the performance of lymph node dissections and the lack of proven oncological survival benefit thereof, surgeons might reconsider the performance of lymphadenectomy during CN,” the investigators wrote.
Other common postoperative complications included infectious and cardiopulmonary issues, which occurred in 42 and 39 patients, respectively.
Predictors of complications
Thrombectomy and adjacent organ removal were significant predictors of intraoperative complications on multivariable analysis. The odds ratios were 1.38 (P = .009) for thrombectomy and 2.71 (P = .004) for adjacent organ removal.
Estimated blood loss was a significant predictor of low- and high-grade postoperative complications. The OR for high-grade complications per 200 mL of blood lost was 1.06 (P = .007), and the OR for low-grade complications per 200 mL blood lost was 1.09 (P = .001).
There was a strong inverse correlation with CN case load at each center and high-grade postoperative complications, which highlights “the impact of centralization of care on postoperative outcomes in complex surgical scenarios,” the investigators wrote. The OR per 25 cases was 0.88 (P = .04).
Results were largely the same when the analysis was limited to the 560 subjects treated since 2006, in the targeted therapy era, except that adjacent organ removal as a predictor of intraoperative complications did not quite reach statistical significance (P = .06).
The presurgery risk factors identified in this study should assist with presurgical counseling, said Zachery Reichert, MD, PhD, a genitourinary medical oncologist and assistant professor at the University of Michigan, Ann Arbor, who was not involved in this study.
“This is especially important for patients who require thrombectomy or adjacent organ removal or do not have access to a surgeon with high cytoreductive nephrectomy caseloads,” he said.
Dr. Reichert reported having no disclosures. There was no external funding for this study, and the investigators didn’t have any disclosures.
SOURCE: Roussel E et al. Eur Urol Oncol. 2020 Aug;3(4):523-9.
according to an analysis of registry data.
Higher intraoperative blood loss was also associated with low-grade postoperative complications. Intraoperative complications were more likely in patients who had concurrent thrombectomy and surgery on adjacent organs.
Eduard Roussel, MD, of University Hospitals Leuven (Belgium) and colleagues reported these findings in European Urology Oncology.
The authors noted that the role of CN in metastatic RCC is controversial. The CARMENA trial, published in the New England Journal of Medicine, “shifted treatment paradigms” away from surgery by suggesting that sunitinib alone is noninferior to sunitinib after CN.
“Nonetheless, there is a general consensus that certain selected subgroups of patients with low-volume, single-site metastases and few adverse IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria would still benefit from the continued use of upfront CN,” the authors wrote.
They advised clinicians to weigh the risks and benefits of CN, particularly because “postoperative morbidity might preclude or delay the use of subsequent systemic therapies.” However, the risk/benefit calculation for CN has been difficult because past investigations have tended to focus only on survival outcomes, so there isn’t much data on morbidity, the authors wrote.
Patient characteristics and complications
To investigate morbidity associated with CN, Dr. Roussel and colleagues reviewed data from the Registry of Metastatic RCC (REMARCC). The team analyzed the clinical records of 736 patients who underwent nephrectomy for metastatic RCC during 1980-2019.
The patients’ median age was 63 years (range, 55-70 years), and about three-quarters were men. The majority had clear cell carcinoma, and the lungs were the most common site of metastases.
More than 97% of procedures were complete nephrectomies, and the rest were partial. The median estimated blood loss was 400 mL, and the median follow-up was 16.5 months.
There were 69 patients who had intraoperative complications, most commonly bleeding (n = 25), spleen laceration (n = 13), and vascular injury (n = 11).
There were 217 patients who had postoperative complications, including 45 patients with high-grade complications (grade 3-5) and 10 who died.
The most common postoperative complications were vascular/lymphatic in nature. These occurred in 67 patients and included 10 lymphoceles.
“[G]iven the relatively high rate of postoperative lymphoceles, which is probably attributable to the performance of lymph node dissections and the lack of proven oncological survival benefit thereof, surgeons might reconsider the performance of lymphadenectomy during CN,” the investigators wrote.
Other common postoperative complications included infectious and cardiopulmonary issues, which occurred in 42 and 39 patients, respectively.
Predictors of complications
Thrombectomy and adjacent organ removal were significant predictors of intraoperative complications on multivariable analysis. The odds ratios were 1.38 (P = .009) for thrombectomy and 2.71 (P = .004) for adjacent organ removal.
Estimated blood loss was a significant predictor of low- and high-grade postoperative complications. The OR for high-grade complications per 200 mL of blood lost was 1.06 (P = .007), and the OR for low-grade complications per 200 mL blood lost was 1.09 (P = .001).
There was a strong inverse correlation with CN case load at each center and high-grade postoperative complications, which highlights “the impact of centralization of care on postoperative outcomes in complex surgical scenarios,” the investigators wrote. The OR per 25 cases was 0.88 (P = .04).
Results were largely the same when the analysis was limited to the 560 subjects treated since 2006, in the targeted therapy era, except that adjacent organ removal as a predictor of intraoperative complications did not quite reach statistical significance (P = .06).
The presurgery risk factors identified in this study should assist with presurgical counseling, said Zachery Reichert, MD, PhD, a genitourinary medical oncologist and assistant professor at the University of Michigan, Ann Arbor, who was not involved in this study.
“This is especially important for patients who require thrombectomy or adjacent organ removal or do not have access to a surgeon with high cytoreductive nephrectomy caseloads,” he said.
Dr. Reichert reported having no disclosures. There was no external funding for this study, and the investigators didn’t have any disclosures.
SOURCE: Roussel E et al. Eur Urol Oncol. 2020 Aug;3(4):523-9.
FROM EUROPEAN UROLOGY ONCOLOGY
Nivo-cabo combo joins advanced RCC treatment ranks
Promoting to the front line two drugs normally used in rearguard action to treat advanced renal cell carcinoma (RCC) – nivolumab (Opdivo) and cabozantinib (Cabometyx) – doubled overall response rates and progression-free survival (PFS) and significantly improved overall survival (OS), compared with first-line sunitinib (Sutent), investigators in the Checkmate 9ER trial reported.
Median PFS among patients with advanced RCC, which was the trial’s primary endpoint, was 16.6 months with nivolumab plus cabozantinib, compared with 8.3 months with sunitinib, translating into a hazard ratio of 0.51 for the combination (P < .0001). The median follow-up was 18.1 months.
Median OS had not been reached in either arm at the time of data cutoff, but the survival curves at the time of the analysis clearly favored nivolumab-cabozatinib, with an HR for death of .060 (P = .0010), said Tony K. Choueri, MD, from the Dana-Farber Cancer Institute in Boston.
“With expanding options in our patients with advanced RCC, the overall efficacy, safety, and quality-of-life benefit, as well as individual patient characteristics, are very important considerations when you select appropriate therapy,” he said in a press briefing prior to his presentation of the data in a presidential symposium at the European Society of Medical Oncology Virtual Congress 2020.
Although the nivolumab-cabozantinib combination therapy looks good, it’s late to the game, commented Dominik Berthold, MD, from the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, the invited discussant for the briefing.
“The question is, what’s the only drawback of this trial? It’s probably the fact that it’s not first in class in this situation,” he said.
Dr. Berthold noted that nivolumab-cabozantinib, if approved for the frontline setting, will join the combination of the tyrosine kinase inhibitor (TKI) axitinib (Inlyta) plus pembrolizumab (Keytruda), which, as previously reported, was associated with a nearly 50% reduction in the risk for death in the KEYNOTE-426 trial. This combination was approved by the Food and Drug Administration for the frontline setting in April 2019.
As shown in the CheckMate-214 study, the combination of the programmed cell death protein–1 (PD-1) inhibitor nivolumab with the CTLA-4 inhibitor ipilimumab (Yervoy) was associated with significantly higher objective response rates and OS rates compared with sunitinib. This combination was approved by the FDA in April 2018 as first-line therapy for patients with advanced intermediate- or poor-risk RCC.
CheckMate 9ER details
A total of 651 patients with previously untreated advanced or metastatic RCC that had a clear cell component in all International Metastatic RCC Database Consortium risk groups were enrolled and randomly assigned to receive either intravenous nivolumab at 240 mg every 2 weeks plus oral cabozantinib at 40 mg daily or oral sunitinib at 50 mg daily in cycles of 4 weeks on therapy/2 weeks off therapy. Patients were treated until disease progression or unacceptable toxicities occurred.
The primary PFS endpoint and the secondary OS endpoint both favored the combination, as did the objective response rate, which was 55.7% with nivolumab-cabozantinib versus 27.1% with sunitinib (P < .0001).
Complete responses were seen in 8% of patients who received the combination versus 4.6% with the patients who received sunitinib. Partial responses were seen in 47.7% and 22.6%, respectively.
Patients generally tolerated the combination. The incidence of the most common high-grade treatment-emergent adverse events and other adverse events of any grade was similar to that seen with sunitinib, Dr. Choueri said.
The rates of treatment-related events that led to discontinuation was 3.1% among patients who received the combination, 5.6% among patients who received the nivolumab component only, and 6.6% among patients who received cabozantinib only. It was 8.8% among patients who received sunitinib. More than 50% of patients in the combination arm needed a dose reduction of nivolumab-cabozantinib because of adverse events, however.
“Overall, it seems that the combination has a somewhat manageable safety profile in patients with advanced RCC,” Dr. Choueri said.
Patient-reported quality of life, as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 total score, was an exploratory endpoint. It was maintained over time with the combination but deteriorated over time with sunitinib, with statistically significant differences between the study arms at most time points to 91 weeks, he reported.
Making choices
Dr. Berthold acknowledged the benefit that having an additional therapy offers clinicians and patients.
“What we still need to learn here is, ‘Are there any patient populations who may benefit more on this combination compared with other combinations?’ ” he said. “Cabozantinib is quite a unique TKI which may target better bone metastases, for example, so I think there are things we need to learn from further data and longer follow-up.”
Camillo Porta, MD, from the University of Bari (Italy), the invited discussant for the presidential symposium, urged caution in comparing the three regimens, owing to differences in the drug used, study endpoints, baseline patient characteristics, and the distribution of patients among different prognostic groups.
When it comes to deciding between frontline regimens, “the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor,” he said.
For patients with highly aggressive disease, the use of an immune checkpoint inhibitor plus a vascular endothelial growth factor receptor (VEGFR)–directed TKI may help control disease long enough to give the checkpoint inhibitor time to work.
“Otherwise, one could head for the long-term benefit of the immune combo as well as for complete responses, trying to spare [patients] the additional toxicities deriving from the continuous use of the VEGFR TKI,” he added.
Dr. Porta noted that when considering the trade-off between efficacy and safety in the first-line setting, many patients are willing to accept more toxicities in exchange for clinical benefit.
The study was sponsored by Bristol-Myers Squibb. Dr. Choueri disclosed consultancy fees, advisory board activity, manuscript preparation, travel/lodging, honoraria, and grants for clinical trials from BMS and others. Dr. Berthold disclosed an advisory role for Ipsen, BMS, Merck, and Pfizer. Dr. Porta disclosed advisory/consulting activities and speakers bureau participation for BMS and others.
This article first appeared on Medscape.com.
Promoting to the front line two drugs normally used in rearguard action to treat advanced renal cell carcinoma (RCC) – nivolumab (Opdivo) and cabozantinib (Cabometyx) – doubled overall response rates and progression-free survival (PFS) and significantly improved overall survival (OS), compared with first-line sunitinib (Sutent), investigators in the Checkmate 9ER trial reported.
Median PFS among patients with advanced RCC, which was the trial’s primary endpoint, was 16.6 months with nivolumab plus cabozantinib, compared with 8.3 months with sunitinib, translating into a hazard ratio of 0.51 for the combination (P < .0001). The median follow-up was 18.1 months.
Median OS had not been reached in either arm at the time of data cutoff, but the survival curves at the time of the analysis clearly favored nivolumab-cabozatinib, with an HR for death of .060 (P = .0010), said Tony K. Choueri, MD, from the Dana-Farber Cancer Institute in Boston.
“With expanding options in our patients with advanced RCC, the overall efficacy, safety, and quality-of-life benefit, as well as individual patient characteristics, are very important considerations when you select appropriate therapy,” he said in a press briefing prior to his presentation of the data in a presidential symposium at the European Society of Medical Oncology Virtual Congress 2020.
Although the nivolumab-cabozantinib combination therapy looks good, it’s late to the game, commented Dominik Berthold, MD, from the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, the invited discussant for the briefing.
“The question is, what’s the only drawback of this trial? It’s probably the fact that it’s not first in class in this situation,” he said.
Dr. Berthold noted that nivolumab-cabozantinib, if approved for the frontline setting, will join the combination of the tyrosine kinase inhibitor (TKI) axitinib (Inlyta) plus pembrolizumab (Keytruda), which, as previously reported, was associated with a nearly 50% reduction in the risk for death in the KEYNOTE-426 trial. This combination was approved by the Food and Drug Administration for the frontline setting in April 2019.
As shown in the CheckMate-214 study, the combination of the programmed cell death protein–1 (PD-1) inhibitor nivolumab with the CTLA-4 inhibitor ipilimumab (Yervoy) was associated with significantly higher objective response rates and OS rates compared with sunitinib. This combination was approved by the FDA in April 2018 as first-line therapy for patients with advanced intermediate- or poor-risk RCC.
CheckMate 9ER details
A total of 651 patients with previously untreated advanced or metastatic RCC that had a clear cell component in all International Metastatic RCC Database Consortium risk groups were enrolled and randomly assigned to receive either intravenous nivolumab at 240 mg every 2 weeks plus oral cabozantinib at 40 mg daily or oral sunitinib at 50 mg daily in cycles of 4 weeks on therapy/2 weeks off therapy. Patients were treated until disease progression or unacceptable toxicities occurred.
The primary PFS endpoint and the secondary OS endpoint both favored the combination, as did the objective response rate, which was 55.7% with nivolumab-cabozantinib versus 27.1% with sunitinib (P < .0001).
Complete responses were seen in 8% of patients who received the combination versus 4.6% with the patients who received sunitinib. Partial responses were seen in 47.7% and 22.6%, respectively.
Patients generally tolerated the combination. The incidence of the most common high-grade treatment-emergent adverse events and other adverse events of any grade was similar to that seen with sunitinib, Dr. Choueri said.
The rates of treatment-related events that led to discontinuation was 3.1% among patients who received the combination, 5.6% among patients who received the nivolumab component only, and 6.6% among patients who received cabozantinib only. It was 8.8% among patients who received sunitinib. More than 50% of patients in the combination arm needed a dose reduction of nivolumab-cabozantinib because of adverse events, however.
“Overall, it seems that the combination has a somewhat manageable safety profile in patients with advanced RCC,” Dr. Choueri said.
Patient-reported quality of life, as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 total score, was an exploratory endpoint. It was maintained over time with the combination but deteriorated over time with sunitinib, with statistically significant differences between the study arms at most time points to 91 weeks, he reported.
Making choices
Dr. Berthold acknowledged the benefit that having an additional therapy offers clinicians and patients.
“What we still need to learn here is, ‘Are there any patient populations who may benefit more on this combination compared with other combinations?’ ” he said. “Cabozantinib is quite a unique TKI which may target better bone metastases, for example, so I think there are things we need to learn from further data and longer follow-up.”
Camillo Porta, MD, from the University of Bari (Italy), the invited discussant for the presidential symposium, urged caution in comparing the three regimens, owing to differences in the drug used, study endpoints, baseline patient characteristics, and the distribution of patients among different prognostic groups.
When it comes to deciding between frontline regimens, “the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor,” he said.
For patients with highly aggressive disease, the use of an immune checkpoint inhibitor plus a vascular endothelial growth factor receptor (VEGFR)–directed TKI may help control disease long enough to give the checkpoint inhibitor time to work.
“Otherwise, one could head for the long-term benefit of the immune combo as well as for complete responses, trying to spare [patients] the additional toxicities deriving from the continuous use of the VEGFR TKI,” he added.
Dr. Porta noted that when considering the trade-off between efficacy and safety in the first-line setting, many patients are willing to accept more toxicities in exchange for clinical benefit.
The study was sponsored by Bristol-Myers Squibb. Dr. Choueri disclosed consultancy fees, advisory board activity, manuscript preparation, travel/lodging, honoraria, and grants for clinical trials from BMS and others. Dr. Berthold disclosed an advisory role for Ipsen, BMS, Merck, and Pfizer. Dr. Porta disclosed advisory/consulting activities and speakers bureau participation for BMS and others.
This article first appeared on Medscape.com.
Promoting to the front line two drugs normally used in rearguard action to treat advanced renal cell carcinoma (RCC) – nivolumab (Opdivo) and cabozantinib (Cabometyx) – doubled overall response rates and progression-free survival (PFS) and significantly improved overall survival (OS), compared with first-line sunitinib (Sutent), investigators in the Checkmate 9ER trial reported.
Median PFS among patients with advanced RCC, which was the trial’s primary endpoint, was 16.6 months with nivolumab plus cabozantinib, compared with 8.3 months with sunitinib, translating into a hazard ratio of 0.51 for the combination (P < .0001). The median follow-up was 18.1 months.
Median OS had not been reached in either arm at the time of data cutoff, but the survival curves at the time of the analysis clearly favored nivolumab-cabozatinib, with an HR for death of .060 (P = .0010), said Tony K. Choueri, MD, from the Dana-Farber Cancer Institute in Boston.
“With expanding options in our patients with advanced RCC, the overall efficacy, safety, and quality-of-life benefit, as well as individual patient characteristics, are very important considerations when you select appropriate therapy,” he said in a press briefing prior to his presentation of the data in a presidential symposium at the European Society of Medical Oncology Virtual Congress 2020.
Although the nivolumab-cabozantinib combination therapy looks good, it’s late to the game, commented Dominik Berthold, MD, from the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, the invited discussant for the briefing.
“The question is, what’s the only drawback of this trial? It’s probably the fact that it’s not first in class in this situation,” he said.
Dr. Berthold noted that nivolumab-cabozantinib, if approved for the frontline setting, will join the combination of the tyrosine kinase inhibitor (TKI) axitinib (Inlyta) plus pembrolizumab (Keytruda), which, as previously reported, was associated with a nearly 50% reduction in the risk for death in the KEYNOTE-426 trial. This combination was approved by the Food and Drug Administration for the frontline setting in April 2019.
As shown in the CheckMate-214 study, the combination of the programmed cell death protein–1 (PD-1) inhibitor nivolumab with the CTLA-4 inhibitor ipilimumab (Yervoy) was associated with significantly higher objective response rates and OS rates compared with sunitinib. This combination was approved by the FDA in April 2018 as first-line therapy for patients with advanced intermediate- or poor-risk RCC.
CheckMate 9ER details
A total of 651 patients with previously untreated advanced or metastatic RCC that had a clear cell component in all International Metastatic RCC Database Consortium risk groups were enrolled and randomly assigned to receive either intravenous nivolumab at 240 mg every 2 weeks plus oral cabozantinib at 40 mg daily or oral sunitinib at 50 mg daily in cycles of 4 weeks on therapy/2 weeks off therapy. Patients were treated until disease progression or unacceptable toxicities occurred.
The primary PFS endpoint and the secondary OS endpoint both favored the combination, as did the objective response rate, which was 55.7% with nivolumab-cabozantinib versus 27.1% with sunitinib (P < .0001).
Complete responses were seen in 8% of patients who received the combination versus 4.6% with the patients who received sunitinib. Partial responses were seen in 47.7% and 22.6%, respectively.
Patients generally tolerated the combination. The incidence of the most common high-grade treatment-emergent adverse events and other adverse events of any grade was similar to that seen with sunitinib, Dr. Choueri said.
The rates of treatment-related events that led to discontinuation was 3.1% among patients who received the combination, 5.6% among patients who received the nivolumab component only, and 6.6% among patients who received cabozantinib only. It was 8.8% among patients who received sunitinib. More than 50% of patients in the combination arm needed a dose reduction of nivolumab-cabozantinib because of adverse events, however.
“Overall, it seems that the combination has a somewhat manageable safety profile in patients with advanced RCC,” Dr. Choueri said.
Patient-reported quality of life, as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 total score, was an exploratory endpoint. It was maintained over time with the combination but deteriorated over time with sunitinib, with statistically significant differences between the study arms at most time points to 91 weeks, he reported.
Making choices
Dr. Berthold acknowledged the benefit that having an additional therapy offers clinicians and patients.
“What we still need to learn here is, ‘Are there any patient populations who may benefit more on this combination compared with other combinations?’ ” he said. “Cabozantinib is quite a unique TKI which may target better bone metastases, for example, so I think there are things we need to learn from further data and longer follow-up.”
Camillo Porta, MD, from the University of Bari (Italy), the invited discussant for the presidential symposium, urged caution in comparing the three regimens, owing to differences in the drug used, study endpoints, baseline patient characteristics, and the distribution of patients among different prognostic groups.
When it comes to deciding between frontline regimens, “the only possible, though highly empiric, driver of our therapeutical choice should be the biological aggressiveness of the tumor,” he said.
For patients with highly aggressive disease, the use of an immune checkpoint inhibitor plus a vascular endothelial growth factor receptor (VEGFR)–directed TKI may help control disease long enough to give the checkpoint inhibitor time to work.
“Otherwise, one could head for the long-term benefit of the immune combo as well as for complete responses, trying to spare [patients] the additional toxicities deriving from the continuous use of the VEGFR TKI,” he added.
Dr. Porta noted that when considering the trade-off between efficacy and safety in the first-line setting, many patients are willing to accept more toxicities in exchange for clinical benefit.
The study was sponsored by Bristol-Myers Squibb. Dr. Choueri disclosed consultancy fees, advisory board activity, manuscript preparation, travel/lodging, honoraria, and grants for clinical trials from BMS and others. Dr. Berthold disclosed an advisory role for Ipsen, BMS, Merck, and Pfizer. Dr. Porta disclosed advisory/consulting activities and speakers bureau participation for BMS and others.
This article first appeared on Medscape.com.
FROM ESMO 2020
Survey quantifies COVID-19’s impact on oncology
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
FROM ESMO 2020
COVID-19 prompts ‘democratization’ of cancer trials
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.
Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.
Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
Trial, administrative, and patient-care modifications
COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.
Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.
Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.
Modifications prompted by the pandemic include the following:
- On-site auditing was suspended.
- Oral investigational agents were shipped directly to patients.
- “Remote” informed consent (telephone or video consenting) was permitted.
- Local providers could perform study-related services, with oversight by the research site.
- Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.
“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
Operational accomplishments and benefits
The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.
However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.
The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.
Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.
Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.
These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.
Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.
“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.
In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
Streamlining trial regulatory processes
In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.
One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.
The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.
Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.
The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
Future directions and challenges
The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.
With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.
“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”
Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.
Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.
On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.
The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
Shared goals and democratization
The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.
Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.
A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.
Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.
Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.
FROM AACR: COVID-19 and Cancer
The march of immunotherapy continues at ESMO 2020
The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.
The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.
John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”
The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.
They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.
“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”
He added: “That was out of the question.”
Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”
Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.
However, there were some benefits from the change.
She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.
“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
Presidential symposia
Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.
He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.
However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.
Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”
On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”
One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.
The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.
The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.
“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.
“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.
This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.
“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.
The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.
Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”
He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.
Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.
Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.
This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.
“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.
“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
Next year
For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.
She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.
This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.
This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.
She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.
“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”
The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.
The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.
John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”
The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.
They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.
“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”
He added: “That was out of the question.”
Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”
Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.
However, there were some benefits from the change.
She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.
“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
Presidential symposia
Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.
He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.
However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.
Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”
On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”
One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.
The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.
The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.
“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.
“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.
This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.
“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.
The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.
Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”
He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.
Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.
Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.
This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.
“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.
“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
Next year
For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.
She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.
This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.
This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.
She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.
“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”
The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The use of immunotherapy for upper gastrointestinal tumors and renal cancer, ALK- and EGFR-targeted agents in non–small cell lung cancer (NSCLC), and the next step in personalized prostate cancer management will all be subjects of headlining presentations at the ESMO Virtual Congress 2020.
The conference will, like so many other major events, be held online this year because of the COVID-19 pandemic.
John B. Haanen, PhD, ESMO 2020 scientific chair, who is from the Netherlands Cancer Institute, Amsterdam, the Netherlands, told Medscape Medical News that, because the congress is being held online this year, fewer abstracts were submitted; nevertheless, “We were very happy to see ... that the quality was very good.”
The number of submissions was not the only problem the organizing committee had to face in transforming the ESMO Congress into a virtual meeting.
They were unable to fit the scientific and educational programs together and so have had to split them over two consecutive weekends. Moreover, many of the sessions were highly interactive and needed to be either adapted or omitted.
“So the program is somewhat different,” Haanen said. He noted that “the presentations were also made shorter, especially on the educational sessions, because...we can’t expect people to sit behind screens for hours listening to long presentations.”
He added: “That was out of the question.”
Haanen is nevertheless hopeful that the virtual meeting will be “very exciting.”
Solange Peters, MD, PhD, ESMO president, who is also affiliated with the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, said in a press conference that it was a “sacrifice” to move ESMO 2020 online and that “there were very sad moments” when deciding on the content.
However, there were some benefits from the change.
She said that all of the ESMO meetings this year have seen “huge” increases in the number of attendees and the geographical span or reach of each of the conferences.
“So suddenly you also realize that, what is one of the missions of ESMO being to convey education globally ... was probably better reached, better achieved with the virtual format,” she commented.
Presidential symposia
Turning to the program, Haanen first picked out the third presidential symposium, which will be held on Monday, September 21. This will focus entirely on upper gastrointestinal tumors in both the adjuvant and metastatic setting.
He said that in recent years, “very little progress has been made” in this area, with treatment mostly consisting of chemotherapy and chemoradiotherapy.
However, this year’s presentations will explore the addition of immunotherapy either to chemotherapy or as an adjuvant treatment following completion of standard-of-care treatment for local disease.
Haanen said that the results will be “very interesting ... and may change current practice,” something that “is very important for both doctors and their patients.”
On Saturday, September 19, the first presidential symposium will include two presentations on lung cancer that Haanen said will offer some “exciting new [results] that I am sure will change clinical practice.”
One will be on the CROWN phase 3 trial comparing lorlatinib and crizotinib in the first-line treatment of patients with advanced ALK-positive NSCLC.
The other will present results on central nervous system disease recurrence from the ADAURA phase 3 trial of osimertinib adjuvant therapy in patients with resected EGFR-mutated NSCLC.
The same session will also see new data in advanced renal cell carcinoma from CheckMate 9ER, in which the c-Met and VEGFR2 inhibitor cabozantinib (Cabometyx) was combined with nivolumab (Opdivo) and compared to sunitinib (Sutent) in untreated patients.
“Last year, there were already some exciting results of the combination of axitinib [Inlyta], either with pembrolizumab [Keytruda] or with avelumab [Bavencio]...in the first-line setting in metastatic clear cell renal cell cancer,” Hannen said.
“Clearly there was a survival advantage over the standard of care, sunitinib,” he added.
This year, not only will efficacy data from CheckMate 9ER be presented but also quality-of-life results.
“That’s very important, because what everybody is afraid of is that, by adding drugs, you always get more impact on the quality of life, but you will see that the quality-of-life results are very exciting,” he said.
The second presidential symposium will feature studies on prostate cancer, notably the phase 3 IPATential150 trial of abiraterone (Zytiga) plus either ipatasertib or placebo in metastatic castration-resistant prostate cancer.
Ipatasertib targets Akt, and Haanen said that “by adding it to, let’s say, standard-of-care treatment ... the question of course of will be, Does that have a better outcome?”
He believes the results will be a “very nice illustration” that prostate cancer management is heading in the direction of personalized treatment.
Alongside the presidential symposia, there will be a number of proffered paper sessions on the latest results in all aspects of oncology, including results from the ASCENT trial in triple-negative breast cancer, as well as a dedicated COVID-19 track.
Haanen said that the ESMO Virtual Congress 2020, coming after the AACR and ASCO annual meetings, has the “advantage” of being able to present the latest outcomes of patients treated with chemotherapy and immunotherapy against the backdrop of the pandemic.
This will include a study from the ESMO Resilience Task Force on the impact of COVID-19 on oncology professionals both in terms of their personal distress and burnout and their job performance.
“I think that is very important,” Haanen said, “especially because the whole thing with COVID-19 is not yet over, and everybody is preparing for a second wave in the fall and winter.
“It may help us give us clues on how we can protect ourselves or each other to prevent burnout or other problems that we as healthcare caregivers face in this difficult period.”
Next year
For next year, Peters remains hopeful that the ESMO 2021 meeting will take place as planned in Paris.
She anticipates that, indeed, ESMO meetings will be able to take place from spring next year.
This will depend on a vaccine for COVID-19 becoming widely available, although oncologists in some countries may still not be able to travel.
This means “starting probably with hybrid formats, with some of the faculty being on site and some not, [and] the same thing for the attendees,” Peters said.
She suggested that, for ESMO Congress 2021 to work as an on-site meeting, it will require at least half or two-thirds of the originally anticipated number of attendees.
“I hope that Paris next year will happen,” Peters said, adding that it “will probably happen with less attendees – that’s fine, but [still] with a large number of faculty and attendees.”
The commentators have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
FROM ESMO 2020
Hair dye and cancer study ‘offers some reassurance’
Findings limited to White women in United States
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Findings limited to White women in United States
Findings limited to White women in United States
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The largest study of its kind has found no positive association between personal use of permanent hair dye and the risk for most cancers and cancer mortality.
The findings come from the Nurses’ Health Study, an ongoing prospective cohort study of more than 117,000 women who have been followed for 36 years and who did not have cancer at baseline.
The findings were published online on September 2 in the BMJ.
The results “offer some reassurance against concerns that personal use of permanent hair dyes might be associated with increased cancer risk or mortality,” write the investigators, with first author Yin Zhang, PhD, of Harvard Medical School, Boston.
The findings, which are limited to White women in the United States, indicate correlation, not causation, the authors emphasize.
Nevertheless, the researchers found an increased risk for some cancers among hair dye users, especially with greater cumulative dose (200 or more uses during the study period). The risk was increased for basal cell carcinoma, breast cancer (specifically, estrogen receptor negative [ER–], progesterone receptor negative [PR–], and hormone receptor negative [ER–, PR–]), and ovarian cancer.
A British expert not involved in the study dismissed these findings. “The reported associations are very weak, and, given the number of associations reported in this manuscript, they are very likely to be chance findings,” commented Paul Pharoah, PhD, professor of cancer epidemiology at the University of Cambridge (England).
“For the cancers where an increase in risk is reported, the results are not compelling. Even if they were real findings, the associations may not be cause-and-effect, and, even if they were causal associations, the magnitude of the effects are so small that any risk would be trivial.
“In short, none of the findings reported in this manuscript suggest that women who use hair dye are putting themselves at increased risk of cancer,” he stated.
A U.S. researcher who has previously coauthored a study suggesting an association between hair dye and breast cancer agreed that the increases in risk reported in this current study are “small.” But they are “of interest,” especially for breast and ovarian cancer, said Alexandra White, PhD, of the National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C.
Hair dyes include compounds that “are not just potential carcinogens but also act as endocrine disruptors,” she said in an interview.
“In both breast and ovarian cancer, we know that hormones play an important part in the etiology ... so it’s biologically plausible that you would see [these associations in the current study],” added Dr. White, who was approached for comment.
However, she added that, even with the “modest” 20%-28% increase in the relative risk for certain breast cancers linked to a heavy cumulative dose of dyes in the current study, “there doesn’t seem to be any strong association with any cancer type.”
But she also pointed out that the most outstanding risk association was among ER–/PR– breast cancers, which are the “most aggressive and difficult to treat,” and thus the new findings are “important.”
Dr. White is the lead author of a 2019 study that received a lot of media attention because it rang an alarm bell about hair dyes and breast cancer risk.
That study concluded that ever using permanent hair dye or hair straighteners was associated with a higher risk for breast cancer than never using them and that this higher risk was especially associated with Black women. However, the study participants were from the prospective Sister Study. The participants in that study had no history of breast cancer, but they each had at least one sister who did. This family history of breast cancer may represent selection bias.
With changes in the 1980s, even safer now?
The study of hair dyes and cancer has “major public health implications” because the use of hair dye is widespread, Dr. Zhang and colleagues write in their article. They estimate that 50% to 80% of women and 10% of men aged 40 years and older in the United States and Europe use hair dye.
Permanent hair dyes “pose the greatest potential concern,” they stated, adding that these account for approximately 80% of hair dyes used in the United States and Europe and an even higher percentage in Asia.
The International Agency for Research on Cancer classifies occupational exposure to hair dyes as probably carcinogenic, but the carcinogenicity resulting from personal use of hair dyes is not classifiable – thus, there is no warning about at-home usage.
Notably, there was “a huge and very important” change in hair dye ingredients in the 1980s after the Food and Drug Administration warned about some chemicals in permanent hair dyes and the cosmetic industry altered their formulas, lead author Dr. Zhang said.
However, the researchers could not analyze use before and after the changes because not enough women reported first use of permanent hair dye after 1980 (only 1890 of 117,200 participants).
“We could expect that the current ingredients should make it safer,” Dr. Zhang said.
Study details
The researchers report that ever-users of permanent hair dyes had no significant increases in risk for solid cancers (n = 20,805; hazard ratio, 0.98, 95% confidence interval, 0.96-1.01) or hematopoietic cancers overall (n = 1,807; HR, 1.00; 95% CI, 0.91-1.10) compared with nonusers.
Additionally, ever-users did not have an increased risk for most specific cancers or cancer-related death (n = 4,860; HR, 0.96; 95% CI, 0.91-1.02).
As noted above, there were some exceptions.
Basal cell carcinoma risk was slightly increased for ever-users (n = 22,560; HR, 1.05; 95% CI, 1.02-1.08). Cumulative dose (a calculation of duration and frequency) was positively associated with risk for ER– breast cancer, PR– breast cancer, ER–/PR– breast cancer, and ovarian cancer, with risk rising in accordance with the total amount of dye.
Notably, at a cumulative dose of ≥200 uses, there was a 20% increase in the relative risk for ER- breast cancer (n = 1521; HR, 1.20; 95% CI, 1.02-1.41; P value for trend, .03). At the same cumulative dose, there was a 28% increase in the relative risk for ER-/PR- breast cancer (n = 1287; HR, 1.28, 95% CI, 1.08-1.52; P value for trend, .006).
In addition, an increased risk for Hodgkin lymphoma was observed, but only for women with naturally dark hair (the calculation was based on 70 women, 24 of whom had dark hair).
In a press statement, senior author Eva Schernhammer, PhD, of Harvard and the Medical University of Vienna, said the results “justify further prospective validation.”
She also explained that there are many variables to consider in this research, including different populations and countries, different susceptibility genotypes, different exposure settings (personal use vs. occupational exposure), and different colors of the permanent hair dyes used (dark dyes vs. light dyes).
Geographic location is a particularly important variable, suggested the study authors.
They pointed out that Europe, but not the United States, banned some individual hair dye ingredients that were considered carcinogenic during both the 1980s and 2000s. One country has even tighter oversight: “The most restrictive regulation of hair dyes exists in Japan, where cosmetic products are considered equivalent to drugs.”
The study was funded by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health. The study authors and Dr. White have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.