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How Long Should Active Surveillance Last?
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Why Lung Cancer Screening Is Not for Everyone
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
What’s Driving the Higher Breast Cancer Death Rate in Black Women?
More women today are surviving breast cancer if it’s caught early, largely because of better screening and more effective and targeted treatments.
However, not everyone has benefited equitably from this progress. Critical gaps in breast cancer outcomes and survival remain for women in racial and ethnic minority groups.
Black women for instance, have a 41% higher death rate from breast cancer compared with White patients. They also have a greater incidence of aggressive disease like triple-negative breast cancer. Native American and Hispanic women, meanwhile, are more likely to be diagnosed with breast cancer at an earlier age than White women and experience more aggressive breast cancers.
In 2023, Farhad Islami, MD, PhD, and his team published an updated analysis of racial/ethnic and socioeconomic disparities in cancer trends based on data from 2014 to 2020. The analysis found that Black women in particular, were the least likely to have an early-stage diagnosis of breast cancer. Localized‐stage breast cancer was diagnosed in 57% of Black women versus 68% of White women.
“Despite substantial progress in cancer prevention, early detection, and treatments, the burden of cancer remains greater among populations that have been historically marginalized, including people of color, people with lower socioeconomic status, and people living in nonmetropolitan areas,” said Dr. Islami, who is senior scientific director of cancer disparity research in the Surveillance & Health Equity Science Department at the American Cancer Society.
The reasons behind outcomes disparities in breast cancer are complex, making solutions challenging, say experts researching racial differences in cancer outcomes.
Among the findings of this research is that breast cancer tests may be contributing to the disparities and misguiding care for some patients of color.
SDH and Screening Rates Differences By Race
A range of factors contribute to racial and ethnic disparities in breast cancer outcomes, said Pamela Ganschow, MD, an associate professor in the Department of Internal Medicine at the University of Illinois Cancer Center in Chicago and part of the university’s Cancer Prevention and Control research program. These include socioeconomic status, access to timely and high-quality care across the cancer control continuum, cultural beliefs, differences in genetic makeup and tumor biology, as well as system biases, such as implicit biases and systemic racism, Dr. Ganschow said.
Dr. Islami adds that gaps in access to cancer prevention, early detection, and treatment are largely rooted in fundamental inequities in social determinants of health (SDH), such as whether a patient has safe housing, transportation, education, job opportunities, income, access to nutritious foods, and language and literacy skills, among others.
Dr. Islami’s analysis, for example, shows that people of color are generally more likely to have lower educational attainment and to experience poverty, food insecurity, and housing insecurity compared with White people. Among people aged 18-64 years, the age-adjusted proportion of individuals with no health insurance in 2021 was also higher among Black (13.7%), American Indian/Alaskan Native (18.7%), and Hispanic (28.7%) patients than among White (7.8%) or Asian (5.9%) people, according to the report.
Competing needs can also get in the way of prioritizing cancer screenings, especially for patients in lower socio-economic populations, Dr. Ganschow said.
“You’ve got people who are working a job or three jobs, just to make ends meet for their family and can’t necessarily take time off to get that done,” she said. “Nor is it prioritized in their head because they’ve got to put a meal on the table.”
But the racial disparities between Black and White women, at least, are not clearly explained by differences between the screening rates..
Of patients who received mammograms 76% were White and 79% were Black, according to another recent study coauthored by Dr. Islami. While Black women appear to have the highest breast cancer screening rates, some data suggest such rates are being overreported.
Lower screening rates were seen in American Indian/Alaska Native (59%), Asian (67%), and Hispanic women (74%).
Biological Differences, Bad Testing Recommendations May Contribute to Poor Outcomes
Differences in biology may be one overlooked internal driver of lower breast cancer survival in Black women.
Researchers at Sanford Burnham Prebys in La Jolla, California, recently analyzed the breast cells of White and Black women, finding significant molecular differences that may be contributing to higher breast cancer mortality rates in Black women.
Investigators analyzed both healthy tissue and tumor tissue from 185 Black women and compared the samples to that of White women. They discovered differences among Black and White women in the way their DNA repair genes are expressed, both in healthy breast tissue and in tumors positive for estrogen receptor breast cancer. Molecular differences were also present in the cellular signals that control how fast cells, including cancer cells, grow.
DNA repair is part of normal cellular function and helps cells recover from damage that can occur during DNA replication or in response to external factors, such as stress.
“One of the first lines of defense, to prevent the cell from becoming a tumor are DNA damage repair pathways,” said Svasti Haricharan, PhD, a coauthor of the study and an assistant professor at Sanford Burnham Prebys. “We know there are many different DNA damage repair pathways that respond to different types of DNA damage. What we didn’t know was that, even in our normal cells, based on your race and ethnicity, you have different levels of DNA repair proteins.”
The study found that many of the proteins associated with endocrine resistance and poor outcomes in breast cancer patients are differently regulated in Black women compared with White woman. These differences contribute to resistance to standard endocrine therapy, Dr. Haricharan said.
“Because we never studied the biology in Black woman, it was just assumed that across all demographics, it must be the same,” she said. “We are not even accounting for the possibility there are likely intrinsic differences for how you will respond to an endocrine treatment.”
Testing and treatment may also be playing a role in worse breast cancer outcomes for Black women.
In an analysis of 73,363 women with early-stage, estrogen receptor–positive breast cancer, investigators found that a common test used to decide the treatment course for patients may be leading to bad recommendations for Black women.
The test, known as the 21-gene breast recurrence score, is the most commonly ordered biomarker test used to guide doctor’s recommendations for patients with estrogen receptor–positive breast cancer, the most common form of cancer in Black women, representing about 70%-80% of cases.
The test helps physicians identify which patients are good candidates for chemo, but the test may underestimate the benefit of chemo for Black women. It ranks some Black women as unlikely to benefit from chemo, when they actually would have benefited, according to the January 2024 study, published in the Journal of the National Comprehensive Cancer Network.
The test gives a score of zero to 100, explains Kent Hoskins, MD, oncology service line medical director at the University of Illinois (UI) Health and director of the Familial Breast Cancer Clinic at UI Health, both in Chicago. The higher the score, the higher the risk and the greater the benefit of chemotherapy. A patient is either above the cut-off score and receives chemo, or is below the cut-off score and does not. In the analysis, investigators found that Black women start improving with chemo at a lower score than White women do.
Dr. Hoskins said the results raise questions about whether the biomarker test should be modified to be more applicable to Black women, whether other tests should be used, or if physicians should judge cut-off scores differently, depending on race.
How Neighborhood Impacts Breast Cancer, Death Rates
Living in a disadvantaged neighborhood also lowers breast cancer survival, according to new research. A disadvantaged neighborhood is generally defined as a location associated with higher concentrations of poverty, higher rates of unemployment, and less access to health care, quality housing, food, and community resources, according to the Centers for Disease Control and Prevention.
Authors of a study published in JAMA Network Open on April 18 identified 350,824 patients with breast cancer. Of these, 41,519 (11.8%) were Hispanic, 39,631 (11.3%) were non-Hispanic Black, and 234,698 (66.9%) were non-Hispanic White. Investigators divided the patients into five groups representing the lowest to highest neighborhood socioeconomic indices using the Yost Index. (The Yost Index is used by the National Cancer Institute for cancer surveillance and is based on variables such as household income, home value, median rent, percentage below 150% of the poverty line, education, and unemployment.)
Of the Black and Hispanic patients in the study, the highest proportions of both demographics lived in the most disadvantaged neighborhoods. (16,141 Black patients [30.9%]) and 10,168 Hispanic patients [19.5%]). Although 45% of White patients also fell into that same category, the highest proportion of White patients in the study lived in the most advantaged neighborhoods (66,529 patients [76.2%]).
Findings showed patients in the most disadvantaged neighborhoods had the highest proportion of triple-negative breast cancer. Patients in this group also had the lowest proportion of patients who completed surgery and radiation, and the highest proportion of patients who received chemotherapy, compared with all other neighborhood groups. The most advantaged neighborhoods group had higher proportions of localized-stage cancer, a higher proportion of patients who underwent surgery and radiation, and the lowest proportion of patients receiving chemotherapy treatment.
Patients in the most disadvantaged neighborhoods also had the highest risk of mortality (hazard ratio [HR,] 1.53; 95% CI, 1.48-1.59; P less than .001) compared with patients living in the most advantaged neighborhoods. Non-Hispanic Black patients in particular, had the highest risk of mortality, compared with non-Hispanic White patients (HR, 1.16; 95% CI, 1.13-1.20; P less than .001).
Authors wrote that the findings suggest neighborhood disadvantage is independently associated with shorter survival in patients with breast cancer, even after controlling for individual-level factors, tumor characteristics, and treatment.
“To address these residual disparities associated with neighborhood disadvantage, research must focus on which components of the built environment influence outcomes,” the authors said.
Another recent study also found correlations among where breast cancer patients lived and how they fared with the disease.
Jasmine M. Miller-Kleinhenz, PhD, an assistant professor at University of Mississippi Medical Center in Jackson, studied how historical redlining impacts breast cancer development and outcomes in her research published in JAMA Network Open, earlier this year. Redlining refers to the practice of denying people access to credit because of where they live. Historically, mortgage lenders widely redlined neighborhoods with predominantly Black residents. The 1968 Fair Housing Act outlawed racially motivated redlining, but consequences from historical redlining still exist.
Dr. Miller-Kleinhenz and her colleagues analyzed a cohort of 1764 women diagnosed with breast cancer between January 2010 and December 2017, who were followed up through December 2019. Investigators accessed the cohort based on three exposures: historic redlining (HRL), contemporary mortgage discrimination (CMD), and persistent mortgage discrimination (PMD). Contemporary mortgage discrimination refers to current-day discriminatory mortgage practices and persistent mortgage discrimination refers to neighborhoods that have experienced both HRL and CMD.
Findings showed that Black women living in historical redlined areas had increased odds of being diagnosed with aggressive forms of breast cancer, while White women in redlined areas had increased odds of late-stage diagnosis.
White women exposed to persistent mortgage discrimination were twice as likely to die of breast cancer, compared with their White counterparts living in areas without historical redlining or contemporary mortgage discrimination, the study found.
That is not to say that Black women did not have an increased risk of breast cancer mortality, Dr. Miller-Kleinhenz explained. Black women had a more than threefold elevated risk of breast cancer mortality compared with White women no matter where they lived, according to the findings.
“These results were surprising because it is showing that while neighborhood conditions might be a major driver of breast cancer mortality in White women, there are factors beyond the neighborhood that are additional drivers that are contributing to poor outcomes in Black women,” she said.
Hope for Improved Outcomes, Higher Survival Rates
Investigators hope the findings of all of this new research lead to better, more targeted treatments and, in turn, improved outcomes.
Dr. Haricharan is optimistic about the improvement of breast cancer outcomes as more is learned about the biology of Black patients and other non-White patients.
There is a growing effort to include more data from minoritized populations in breast cancer research studies, Dr. Haricharan said, and she foresees associated changes to clinical protocols in the future. Her own team is working on creating larger data sets that are more representative of non-White patients to further analyze the differences found in their prior study.
“I think there’s this understanding that, until we have data sets that are more representative, we really are catering to [only one] population in terms of our diagnostic and therapeutic technological advances,” she said.
The American Cancer Society meanwhile, is launching a new initiative in May that aims to collect more health data from Black women to ultimately develop more effective cancer interventions. VOICES of Black Women will focus on collecting and studying health data from Black women through online surveys. The society’s goal is to enroll at least 100,000 Black women in the United States between ages 25 and 55.
Dr. Miller-Kleinhenz called the initiative “an important step to starting to research and answer some of these lingering questions about why there continue to be breast cancer disparities.”
More women today are surviving breast cancer if it’s caught early, largely because of better screening and more effective and targeted treatments.
However, not everyone has benefited equitably from this progress. Critical gaps in breast cancer outcomes and survival remain for women in racial and ethnic minority groups.
Black women for instance, have a 41% higher death rate from breast cancer compared with White patients. They also have a greater incidence of aggressive disease like triple-negative breast cancer. Native American and Hispanic women, meanwhile, are more likely to be diagnosed with breast cancer at an earlier age than White women and experience more aggressive breast cancers.
In 2023, Farhad Islami, MD, PhD, and his team published an updated analysis of racial/ethnic and socioeconomic disparities in cancer trends based on data from 2014 to 2020. The analysis found that Black women in particular, were the least likely to have an early-stage diagnosis of breast cancer. Localized‐stage breast cancer was diagnosed in 57% of Black women versus 68% of White women.
“Despite substantial progress in cancer prevention, early detection, and treatments, the burden of cancer remains greater among populations that have been historically marginalized, including people of color, people with lower socioeconomic status, and people living in nonmetropolitan areas,” said Dr. Islami, who is senior scientific director of cancer disparity research in the Surveillance & Health Equity Science Department at the American Cancer Society.
The reasons behind outcomes disparities in breast cancer are complex, making solutions challenging, say experts researching racial differences in cancer outcomes.
Among the findings of this research is that breast cancer tests may be contributing to the disparities and misguiding care for some patients of color.
SDH and Screening Rates Differences By Race
A range of factors contribute to racial and ethnic disparities in breast cancer outcomes, said Pamela Ganschow, MD, an associate professor in the Department of Internal Medicine at the University of Illinois Cancer Center in Chicago and part of the university’s Cancer Prevention and Control research program. These include socioeconomic status, access to timely and high-quality care across the cancer control continuum, cultural beliefs, differences in genetic makeup and tumor biology, as well as system biases, such as implicit biases and systemic racism, Dr. Ganschow said.
Dr. Islami adds that gaps in access to cancer prevention, early detection, and treatment are largely rooted in fundamental inequities in social determinants of health (SDH), such as whether a patient has safe housing, transportation, education, job opportunities, income, access to nutritious foods, and language and literacy skills, among others.
Dr. Islami’s analysis, for example, shows that people of color are generally more likely to have lower educational attainment and to experience poverty, food insecurity, and housing insecurity compared with White people. Among people aged 18-64 years, the age-adjusted proportion of individuals with no health insurance in 2021 was also higher among Black (13.7%), American Indian/Alaskan Native (18.7%), and Hispanic (28.7%) patients than among White (7.8%) or Asian (5.9%) people, according to the report.
Competing needs can also get in the way of prioritizing cancer screenings, especially for patients in lower socio-economic populations, Dr. Ganschow said.
“You’ve got people who are working a job or three jobs, just to make ends meet for their family and can’t necessarily take time off to get that done,” she said. “Nor is it prioritized in their head because they’ve got to put a meal on the table.”
But the racial disparities between Black and White women, at least, are not clearly explained by differences between the screening rates..
Of patients who received mammograms 76% were White and 79% were Black, according to another recent study coauthored by Dr. Islami. While Black women appear to have the highest breast cancer screening rates, some data suggest such rates are being overreported.
Lower screening rates were seen in American Indian/Alaska Native (59%), Asian (67%), and Hispanic women (74%).
Biological Differences, Bad Testing Recommendations May Contribute to Poor Outcomes
Differences in biology may be one overlooked internal driver of lower breast cancer survival in Black women.
Researchers at Sanford Burnham Prebys in La Jolla, California, recently analyzed the breast cells of White and Black women, finding significant molecular differences that may be contributing to higher breast cancer mortality rates in Black women.
Investigators analyzed both healthy tissue and tumor tissue from 185 Black women and compared the samples to that of White women. They discovered differences among Black and White women in the way their DNA repair genes are expressed, both in healthy breast tissue and in tumors positive for estrogen receptor breast cancer. Molecular differences were also present in the cellular signals that control how fast cells, including cancer cells, grow.
DNA repair is part of normal cellular function and helps cells recover from damage that can occur during DNA replication or in response to external factors, such as stress.
“One of the first lines of defense, to prevent the cell from becoming a tumor are DNA damage repair pathways,” said Svasti Haricharan, PhD, a coauthor of the study and an assistant professor at Sanford Burnham Prebys. “We know there are many different DNA damage repair pathways that respond to different types of DNA damage. What we didn’t know was that, even in our normal cells, based on your race and ethnicity, you have different levels of DNA repair proteins.”
The study found that many of the proteins associated with endocrine resistance and poor outcomes in breast cancer patients are differently regulated in Black women compared with White woman. These differences contribute to resistance to standard endocrine therapy, Dr. Haricharan said.
“Because we never studied the biology in Black woman, it was just assumed that across all demographics, it must be the same,” she said. “We are not even accounting for the possibility there are likely intrinsic differences for how you will respond to an endocrine treatment.”
Testing and treatment may also be playing a role in worse breast cancer outcomes for Black women.
In an analysis of 73,363 women with early-stage, estrogen receptor–positive breast cancer, investigators found that a common test used to decide the treatment course for patients may be leading to bad recommendations for Black women.
The test, known as the 21-gene breast recurrence score, is the most commonly ordered biomarker test used to guide doctor’s recommendations for patients with estrogen receptor–positive breast cancer, the most common form of cancer in Black women, representing about 70%-80% of cases.
The test helps physicians identify which patients are good candidates for chemo, but the test may underestimate the benefit of chemo for Black women. It ranks some Black women as unlikely to benefit from chemo, when they actually would have benefited, according to the January 2024 study, published in the Journal of the National Comprehensive Cancer Network.
The test gives a score of zero to 100, explains Kent Hoskins, MD, oncology service line medical director at the University of Illinois (UI) Health and director of the Familial Breast Cancer Clinic at UI Health, both in Chicago. The higher the score, the higher the risk and the greater the benefit of chemotherapy. A patient is either above the cut-off score and receives chemo, or is below the cut-off score and does not. In the analysis, investigators found that Black women start improving with chemo at a lower score than White women do.
Dr. Hoskins said the results raise questions about whether the biomarker test should be modified to be more applicable to Black women, whether other tests should be used, or if physicians should judge cut-off scores differently, depending on race.
How Neighborhood Impacts Breast Cancer, Death Rates
Living in a disadvantaged neighborhood also lowers breast cancer survival, according to new research. A disadvantaged neighborhood is generally defined as a location associated with higher concentrations of poverty, higher rates of unemployment, and less access to health care, quality housing, food, and community resources, according to the Centers for Disease Control and Prevention.
Authors of a study published in JAMA Network Open on April 18 identified 350,824 patients with breast cancer. Of these, 41,519 (11.8%) were Hispanic, 39,631 (11.3%) were non-Hispanic Black, and 234,698 (66.9%) were non-Hispanic White. Investigators divided the patients into five groups representing the lowest to highest neighborhood socioeconomic indices using the Yost Index. (The Yost Index is used by the National Cancer Institute for cancer surveillance and is based on variables such as household income, home value, median rent, percentage below 150% of the poverty line, education, and unemployment.)
Of the Black and Hispanic patients in the study, the highest proportions of both demographics lived in the most disadvantaged neighborhoods. (16,141 Black patients [30.9%]) and 10,168 Hispanic patients [19.5%]). Although 45% of White patients also fell into that same category, the highest proportion of White patients in the study lived in the most advantaged neighborhoods (66,529 patients [76.2%]).
Findings showed patients in the most disadvantaged neighborhoods had the highest proportion of triple-negative breast cancer. Patients in this group also had the lowest proportion of patients who completed surgery and radiation, and the highest proportion of patients who received chemotherapy, compared with all other neighborhood groups. The most advantaged neighborhoods group had higher proportions of localized-stage cancer, a higher proportion of patients who underwent surgery and radiation, and the lowest proportion of patients receiving chemotherapy treatment.
Patients in the most disadvantaged neighborhoods also had the highest risk of mortality (hazard ratio [HR,] 1.53; 95% CI, 1.48-1.59; P less than .001) compared with patients living in the most advantaged neighborhoods. Non-Hispanic Black patients in particular, had the highest risk of mortality, compared with non-Hispanic White patients (HR, 1.16; 95% CI, 1.13-1.20; P less than .001).
Authors wrote that the findings suggest neighborhood disadvantage is independently associated with shorter survival in patients with breast cancer, even after controlling for individual-level factors, tumor characteristics, and treatment.
“To address these residual disparities associated with neighborhood disadvantage, research must focus on which components of the built environment influence outcomes,” the authors said.
Another recent study also found correlations among where breast cancer patients lived and how they fared with the disease.
Jasmine M. Miller-Kleinhenz, PhD, an assistant professor at University of Mississippi Medical Center in Jackson, studied how historical redlining impacts breast cancer development and outcomes in her research published in JAMA Network Open, earlier this year. Redlining refers to the practice of denying people access to credit because of where they live. Historically, mortgage lenders widely redlined neighborhoods with predominantly Black residents. The 1968 Fair Housing Act outlawed racially motivated redlining, but consequences from historical redlining still exist.
Dr. Miller-Kleinhenz and her colleagues analyzed a cohort of 1764 women diagnosed with breast cancer between January 2010 and December 2017, who were followed up through December 2019. Investigators accessed the cohort based on three exposures: historic redlining (HRL), contemporary mortgage discrimination (CMD), and persistent mortgage discrimination (PMD). Contemporary mortgage discrimination refers to current-day discriminatory mortgage practices and persistent mortgage discrimination refers to neighborhoods that have experienced both HRL and CMD.
Findings showed that Black women living in historical redlined areas had increased odds of being diagnosed with aggressive forms of breast cancer, while White women in redlined areas had increased odds of late-stage diagnosis.
White women exposed to persistent mortgage discrimination were twice as likely to die of breast cancer, compared with their White counterparts living in areas without historical redlining or contemporary mortgage discrimination, the study found.
That is not to say that Black women did not have an increased risk of breast cancer mortality, Dr. Miller-Kleinhenz explained. Black women had a more than threefold elevated risk of breast cancer mortality compared with White women no matter where they lived, according to the findings.
“These results were surprising because it is showing that while neighborhood conditions might be a major driver of breast cancer mortality in White women, there are factors beyond the neighborhood that are additional drivers that are contributing to poor outcomes in Black women,” she said.
Hope for Improved Outcomes, Higher Survival Rates
Investigators hope the findings of all of this new research lead to better, more targeted treatments and, in turn, improved outcomes.
Dr. Haricharan is optimistic about the improvement of breast cancer outcomes as more is learned about the biology of Black patients and other non-White patients.
There is a growing effort to include more data from minoritized populations in breast cancer research studies, Dr. Haricharan said, and she foresees associated changes to clinical protocols in the future. Her own team is working on creating larger data sets that are more representative of non-White patients to further analyze the differences found in their prior study.
“I think there’s this understanding that, until we have data sets that are more representative, we really are catering to [only one] population in terms of our diagnostic and therapeutic technological advances,” she said.
The American Cancer Society meanwhile, is launching a new initiative in May that aims to collect more health data from Black women to ultimately develop more effective cancer interventions. VOICES of Black Women will focus on collecting and studying health data from Black women through online surveys. The society’s goal is to enroll at least 100,000 Black women in the United States between ages 25 and 55.
Dr. Miller-Kleinhenz called the initiative “an important step to starting to research and answer some of these lingering questions about why there continue to be breast cancer disparities.”
More women today are surviving breast cancer if it’s caught early, largely because of better screening and more effective and targeted treatments.
However, not everyone has benefited equitably from this progress. Critical gaps in breast cancer outcomes and survival remain for women in racial and ethnic minority groups.
Black women for instance, have a 41% higher death rate from breast cancer compared with White patients. They also have a greater incidence of aggressive disease like triple-negative breast cancer. Native American and Hispanic women, meanwhile, are more likely to be diagnosed with breast cancer at an earlier age than White women and experience more aggressive breast cancers.
In 2023, Farhad Islami, MD, PhD, and his team published an updated analysis of racial/ethnic and socioeconomic disparities in cancer trends based on data from 2014 to 2020. The analysis found that Black women in particular, were the least likely to have an early-stage diagnosis of breast cancer. Localized‐stage breast cancer was diagnosed in 57% of Black women versus 68% of White women.
“Despite substantial progress in cancer prevention, early detection, and treatments, the burden of cancer remains greater among populations that have been historically marginalized, including people of color, people with lower socioeconomic status, and people living in nonmetropolitan areas,” said Dr. Islami, who is senior scientific director of cancer disparity research in the Surveillance & Health Equity Science Department at the American Cancer Society.
The reasons behind outcomes disparities in breast cancer are complex, making solutions challenging, say experts researching racial differences in cancer outcomes.
Among the findings of this research is that breast cancer tests may be contributing to the disparities and misguiding care for some patients of color.
SDH and Screening Rates Differences By Race
A range of factors contribute to racial and ethnic disparities in breast cancer outcomes, said Pamela Ganschow, MD, an associate professor in the Department of Internal Medicine at the University of Illinois Cancer Center in Chicago and part of the university’s Cancer Prevention and Control research program. These include socioeconomic status, access to timely and high-quality care across the cancer control continuum, cultural beliefs, differences in genetic makeup and tumor biology, as well as system biases, such as implicit biases and systemic racism, Dr. Ganschow said.
Dr. Islami adds that gaps in access to cancer prevention, early detection, and treatment are largely rooted in fundamental inequities in social determinants of health (SDH), such as whether a patient has safe housing, transportation, education, job opportunities, income, access to nutritious foods, and language and literacy skills, among others.
Dr. Islami’s analysis, for example, shows that people of color are generally more likely to have lower educational attainment and to experience poverty, food insecurity, and housing insecurity compared with White people. Among people aged 18-64 years, the age-adjusted proportion of individuals with no health insurance in 2021 was also higher among Black (13.7%), American Indian/Alaskan Native (18.7%), and Hispanic (28.7%) patients than among White (7.8%) or Asian (5.9%) people, according to the report.
Competing needs can also get in the way of prioritizing cancer screenings, especially for patients in lower socio-economic populations, Dr. Ganschow said.
“You’ve got people who are working a job or three jobs, just to make ends meet for their family and can’t necessarily take time off to get that done,” she said. “Nor is it prioritized in their head because they’ve got to put a meal on the table.”
But the racial disparities between Black and White women, at least, are not clearly explained by differences between the screening rates..
Of patients who received mammograms 76% were White and 79% were Black, according to another recent study coauthored by Dr. Islami. While Black women appear to have the highest breast cancer screening rates, some data suggest such rates are being overreported.
Lower screening rates were seen in American Indian/Alaska Native (59%), Asian (67%), and Hispanic women (74%).
Biological Differences, Bad Testing Recommendations May Contribute to Poor Outcomes
Differences in biology may be one overlooked internal driver of lower breast cancer survival in Black women.
Researchers at Sanford Burnham Prebys in La Jolla, California, recently analyzed the breast cells of White and Black women, finding significant molecular differences that may be contributing to higher breast cancer mortality rates in Black women.
Investigators analyzed both healthy tissue and tumor tissue from 185 Black women and compared the samples to that of White women. They discovered differences among Black and White women in the way their DNA repair genes are expressed, both in healthy breast tissue and in tumors positive for estrogen receptor breast cancer. Molecular differences were also present in the cellular signals that control how fast cells, including cancer cells, grow.
DNA repair is part of normal cellular function and helps cells recover from damage that can occur during DNA replication or in response to external factors, such as stress.
“One of the first lines of defense, to prevent the cell from becoming a tumor are DNA damage repair pathways,” said Svasti Haricharan, PhD, a coauthor of the study and an assistant professor at Sanford Burnham Prebys. “We know there are many different DNA damage repair pathways that respond to different types of DNA damage. What we didn’t know was that, even in our normal cells, based on your race and ethnicity, you have different levels of DNA repair proteins.”
The study found that many of the proteins associated with endocrine resistance and poor outcomes in breast cancer patients are differently regulated in Black women compared with White woman. These differences contribute to resistance to standard endocrine therapy, Dr. Haricharan said.
“Because we never studied the biology in Black woman, it was just assumed that across all demographics, it must be the same,” she said. “We are not even accounting for the possibility there are likely intrinsic differences for how you will respond to an endocrine treatment.”
Testing and treatment may also be playing a role in worse breast cancer outcomes for Black women.
In an analysis of 73,363 women with early-stage, estrogen receptor–positive breast cancer, investigators found that a common test used to decide the treatment course for patients may be leading to bad recommendations for Black women.
The test, known as the 21-gene breast recurrence score, is the most commonly ordered biomarker test used to guide doctor’s recommendations for patients with estrogen receptor–positive breast cancer, the most common form of cancer in Black women, representing about 70%-80% of cases.
The test helps physicians identify which patients are good candidates for chemo, but the test may underestimate the benefit of chemo for Black women. It ranks some Black women as unlikely to benefit from chemo, when they actually would have benefited, according to the January 2024 study, published in the Journal of the National Comprehensive Cancer Network.
The test gives a score of zero to 100, explains Kent Hoskins, MD, oncology service line medical director at the University of Illinois (UI) Health and director of the Familial Breast Cancer Clinic at UI Health, both in Chicago. The higher the score, the higher the risk and the greater the benefit of chemotherapy. A patient is either above the cut-off score and receives chemo, or is below the cut-off score and does not. In the analysis, investigators found that Black women start improving with chemo at a lower score than White women do.
Dr. Hoskins said the results raise questions about whether the biomarker test should be modified to be more applicable to Black women, whether other tests should be used, or if physicians should judge cut-off scores differently, depending on race.
How Neighborhood Impacts Breast Cancer, Death Rates
Living in a disadvantaged neighborhood also lowers breast cancer survival, according to new research. A disadvantaged neighborhood is generally defined as a location associated with higher concentrations of poverty, higher rates of unemployment, and less access to health care, quality housing, food, and community resources, according to the Centers for Disease Control and Prevention.
Authors of a study published in JAMA Network Open on April 18 identified 350,824 patients with breast cancer. Of these, 41,519 (11.8%) were Hispanic, 39,631 (11.3%) were non-Hispanic Black, and 234,698 (66.9%) were non-Hispanic White. Investigators divided the patients into five groups representing the lowest to highest neighborhood socioeconomic indices using the Yost Index. (The Yost Index is used by the National Cancer Institute for cancer surveillance and is based on variables such as household income, home value, median rent, percentage below 150% of the poverty line, education, and unemployment.)
Of the Black and Hispanic patients in the study, the highest proportions of both demographics lived in the most disadvantaged neighborhoods. (16,141 Black patients [30.9%]) and 10,168 Hispanic patients [19.5%]). Although 45% of White patients also fell into that same category, the highest proportion of White patients in the study lived in the most advantaged neighborhoods (66,529 patients [76.2%]).
Findings showed patients in the most disadvantaged neighborhoods had the highest proportion of triple-negative breast cancer. Patients in this group also had the lowest proportion of patients who completed surgery and radiation, and the highest proportion of patients who received chemotherapy, compared with all other neighborhood groups. The most advantaged neighborhoods group had higher proportions of localized-stage cancer, a higher proportion of patients who underwent surgery and radiation, and the lowest proportion of patients receiving chemotherapy treatment.
Patients in the most disadvantaged neighborhoods also had the highest risk of mortality (hazard ratio [HR,] 1.53; 95% CI, 1.48-1.59; P less than .001) compared with patients living in the most advantaged neighborhoods. Non-Hispanic Black patients in particular, had the highest risk of mortality, compared with non-Hispanic White patients (HR, 1.16; 95% CI, 1.13-1.20; P less than .001).
Authors wrote that the findings suggest neighborhood disadvantage is independently associated with shorter survival in patients with breast cancer, even after controlling for individual-level factors, tumor characteristics, and treatment.
“To address these residual disparities associated with neighborhood disadvantage, research must focus on which components of the built environment influence outcomes,” the authors said.
Another recent study also found correlations among where breast cancer patients lived and how they fared with the disease.
Jasmine M. Miller-Kleinhenz, PhD, an assistant professor at University of Mississippi Medical Center in Jackson, studied how historical redlining impacts breast cancer development and outcomes in her research published in JAMA Network Open, earlier this year. Redlining refers to the practice of denying people access to credit because of where they live. Historically, mortgage lenders widely redlined neighborhoods with predominantly Black residents. The 1968 Fair Housing Act outlawed racially motivated redlining, but consequences from historical redlining still exist.
Dr. Miller-Kleinhenz and her colleagues analyzed a cohort of 1764 women diagnosed with breast cancer between January 2010 and December 2017, who were followed up through December 2019. Investigators accessed the cohort based on three exposures: historic redlining (HRL), contemporary mortgage discrimination (CMD), and persistent mortgage discrimination (PMD). Contemporary mortgage discrimination refers to current-day discriminatory mortgage practices and persistent mortgage discrimination refers to neighborhoods that have experienced both HRL and CMD.
Findings showed that Black women living in historical redlined areas had increased odds of being diagnosed with aggressive forms of breast cancer, while White women in redlined areas had increased odds of late-stage diagnosis.
White women exposed to persistent mortgage discrimination were twice as likely to die of breast cancer, compared with their White counterparts living in areas without historical redlining or contemporary mortgage discrimination, the study found.
That is not to say that Black women did not have an increased risk of breast cancer mortality, Dr. Miller-Kleinhenz explained. Black women had a more than threefold elevated risk of breast cancer mortality compared with White women no matter where they lived, according to the findings.
“These results were surprising because it is showing that while neighborhood conditions might be a major driver of breast cancer mortality in White women, there are factors beyond the neighborhood that are additional drivers that are contributing to poor outcomes in Black women,” she said.
Hope for Improved Outcomes, Higher Survival Rates
Investigators hope the findings of all of this new research lead to better, more targeted treatments and, in turn, improved outcomes.
Dr. Haricharan is optimistic about the improvement of breast cancer outcomes as more is learned about the biology of Black patients and other non-White patients.
There is a growing effort to include more data from minoritized populations in breast cancer research studies, Dr. Haricharan said, and she foresees associated changes to clinical protocols in the future. Her own team is working on creating larger data sets that are more representative of non-White patients to further analyze the differences found in their prior study.
“I think there’s this understanding that, until we have data sets that are more representative, we really are catering to [only one] population in terms of our diagnostic and therapeutic technological advances,” she said.
The American Cancer Society meanwhile, is launching a new initiative in May that aims to collect more health data from Black women to ultimately develop more effective cancer interventions. VOICES of Black Women will focus on collecting and studying health data from Black women through online surveys. The society’s goal is to enroll at least 100,000 Black women in the United States between ages 25 and 55.
Dr. Miller-Kleinhenz called the initiative “an important step to starting to research and answer some of these lingering questions about why there continue to be breast cancer disparities.”
Microbial Signature of KRAS-Mutated Colorectal Cancer Identified
Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.
“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement.
The research was recently published online in Microbiology Spectrum.
The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear.
To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC.
The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.
At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group.
Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.
Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development.
Similarly, Shewanella has been proven to be a contributor to CRC development.
The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.
In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group.
Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic.
The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.
Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.
“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.
Promising Predictive Model
Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC.
The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote.
They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings.
The study had no commercial funding. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.
“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement.
The research was recently published online in Microbiology Spectrum.
The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear.
To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC.
The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.
At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group.
Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.
Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development.
Similarly, Shewanella has been proven to be a contributor to CRC development.
The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.
In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group.
Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic.
The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.
Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.
“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.
Promising Predictive Model
Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC.
The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote.
They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings.
The study had no commercial funding. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Their findings suggest that the gut microbes may serve as noninvasive biomarkers to help identify subtypes of CRC and guide personalized treatment recommendations.
“Our new work contributes to the growing body of evidence highlighting the significance of microbiota-driven mechanisms in cancer pathogenesis,” lead investigator Weizhong Tang, MD, with Guangxi Medical University Cancer Hospital in Nanning, China, said in a statement.
The research was recently published online in Microbiology Spectrum.
The onset and growth of CRC has been linked both to imbalances in the gut microbiome and to mutations in the KRAS gene — about 40% of people with CRC have a KRAS mutation. Yet, the interplay between gut dysbiosis and KRAS mutations in CRC remains unclear.
To investigate further, Dr. Tang and colleagues used 16s rRNA sequencing to analyze stool samples from 94 patients with CRC, including 24 with KRAS-mutated CRC and 70 with KRAS wild-type (nonmutated) CRC.
The researchers identified 26 distinct types of gut microbiota with statistically significant differences in abundance between the KRAS mutant and KRAS wild-type CRC patients.
At the genus level, Fusobacterium, Clostridium, and Shewanella were all abundant in the KRAS mutant group.
Fusobacterium is a Gram-negative microbe found in the gastrointestinal tract and the oral cavity. Recent studies have established a strong link between Fusobacterium and CRC development. Other work found elevated levels of Fusobacterium nucleatum were not only closely associated with KRAS mutation but also correlated with chemoresistance in CRC.
Clostridium produces metabolites in the large intestine, which are known to cause DNA damage and trigger inflammatory responses, thereby increasing the risk of CRC development.
Similarly, Shewanella has been proven to be a contributor to CRC development.
The researchers say it’s “plausible” to consider all three as potential noninvasive biomarkers for identifying KRAS mutation in CRC patients.
In contrast, Bifidobacterium and Akkermansia were abundant in the KRAS wild-type group.
Bifidobacterium is a probiotic with antitumor activity and Akkermansia is a Gram-negative anaerobic bacterium abundant in the gut and currently recognized as a potential probiotic.
The researchers speculated that CRC patients may have a reduced likelihood of developing KRAS mutation in the presence of Bifidobacterium and Akkermansia.
Analyses of biological pathways of gut microbiota associated with KRAS mutation status in CRC revealed a significantly higher abundance of the isoflavonoid biosynthesis pathway in the KRAS wild-type group compared with the KRAS mutant group.
“In comparison to KRAS mutant CRC, it is postulated that KRAS wild-type CRC may be less aggressive due to the upregulation of the isoflavonoid biosynthesis pathway, which may inhibit CRC development and progression,” the authors wrote.
Promising Predictive Model
Dr. Tang and colleagues also developed a machine learning model to predict KRAS mutation status in CRC patients based on the gut microbiota signature in KRAS mutant CRC.
The initial results underscore the model’s predictive efficacy and suggest that it has “considerable potential for clinical application, offering a novel dimension in the prediction of KRAS mutation status among CRC patients in a clinical setting,” the authors wrote.
They caution that the model requires data from a larger cohort to improve its efficacy, and they plan to do larger studies to validate the findings.
The study had no commercial funding. The authors declared no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Certain Women May Face Higher Risk for Second Breast Cancer
TOPLINE:
METHODOLOGY:
- Women who are diagnosed with breast cancer at age 40 or younger are about two to three times more likely to develop second primary breast cancer compared with women who are older when first diagnosed.
- However, data are lacking on whether certain factors increase a woman’s risk for a second primary breast cancer.
- To classify the risk of developing a second primary breast cancer, the researchers evaluated a main cohort of 685 patients with stages 0-III breast cancer who were diagnosed at age 40 years or younger and had undergone unilateral mastectomy or lumpectomy as primary surgery between August 2006 and June 2015. The team also analyzed data on 547 younger women who had a bilateral mastectomy.
- The researchers assessed various breast cancer risk factors, including self-reported ethnicity, race, age, family history of breast or ovarian cancer, germline genetics, tumor stage, grade, and receptor status.
- The primary outcome was the diagnosis of a second primary breast cancer that occurred at least 6 months after the initial diagnosis of primary breast cancer.
TAKEAWAY:
- Among the 685 main study participants, 17 (2.5%) developed a second primary breast cancer (15 contralateral and 2 ipsilateral) over a median of 4.2 years since their primary diagnosis. The 5- and 10-year cumulative incidence of a second primary breast cancer was 1.5% and 2.6%, respectively.
- Overall, only 33 women were positive for a germline pathogenic variant, and having a pathogenic variant was associated with a fourfold higher risk for second primary breast cancer compared with noncarriers at 5 years (5.5% vs 1.3%) and at 10 years (8.9% vs 2.2%). These findings were held in multivariate models.
- Patients initially diagnosed with in situ disease had more than a fivefold higher risk for second primary breast cancer compared with those initially diagnosed with invasive disease — 6.2% vs 1.2% at 5 years and 10.4% vs 2.1% at 10 years (hazard ratio, 5.25; P = .004). These findings were held in multivariate models (adjusted sub-hazard ratio [sHR], 5.61; 95% CI, 1.52-20.70) and among women without a pathogenic variant (adjusted sHR, 5.67; 95% CI, 1.54-20.90).
- The researchers also found a low risk for contralateral breast cancer among women without pathogenic variants, which could inform surgical decision-making.
IN PRACTICE:
Although the number of women positive for a germline pathogenic variant was small (n = 33) and “results should be interpreted cautiously,” the analysis signals “the importance of genetic testing” in younger breast cancer survivors to gauge their risk for a second primary breast cancer, the authors concluded. The authors added that their “finding of a higher risk of [second primary breast cancer] among those diagnosed with in situ primary [breast cancer] merits further investigation.”
SOURCE:
This study, led by Kristen D. Brantley, PhD, from Harvard T. H. Chan School of Public Health, Boston, was published online in JAMA Oncology.
LIMITATIONS:
A small number of second breast cancer events limited the authors’ ability to assess the effects of multiple risk factors together. Data on risk factors might be incomplete. About 9% of participants completed abbreviated questionnaires that did not include information on body mass index, alcohol, smoking, and family history. Frequencies of pathogenic variants besides BRCA1 and BRCA2 may be underestimated.
DISCLOSURES:
This study received no external funding. Four authors reported receiving grants or royalties outside this work. Other reported no competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Women who are diagnosed with breast cancer at age 40 or younger are about two to three times more likely to develop second primary breast cancer compared with women who are older when first diagnosed.
- However, data are lacking on whether certain factors increase a woman’s risk for a second primary breast cancer.
- To classify the risk of developing a second primary breast cancer, the researchers evaluated a main cohort of 685 patients with stages 0-III breast cancer who were diagnosed at age 40 years or younger and had undergone unilateral mastectomy or lumpectomy as primary surgery between August 2006 and June 2015. The team also analyzed data on 547 younger women who had a bilateral mastectomy.
- The researchers assessed various breast cancer risk factors, including self-reported ethnicity, race, age, family history of breast or ovarian cancer, germline genetics, tumor stage, grade, and receptor status.
- The primary outcome was the diagnosis of a second primary breast cancer that occurred at least 6 months after the initial diagnosis of primary breast cancer.
TAKEAWAY:
- Among the 685 main study participants, 17 (2.5%) developed a second primary breast cancer (15 contralateral and 2 ipsilateral) over a median of 4.2 years since their primary diagnosis. The 5- and 10-year cumulative incidence of a second primary breast cancer was 1.5% and 2.6%, respectively.
- Overall, only 33 women were positive for a germline pathogenic variant, and having a pathogenic variant was associated with a fourfold higher risk for second primary breast cancer compared with noncarriers at 5 years (5.5% vs 1.3%) and at 10 years (8.9% vs 2.2%). These findings were held in multivariate models.
- Patients initially diagnosed with in situ disease had more than a fivefold higher risk for second primary breast cancer compared with those initially diagnosed with invasive disease — 6.2% vs 1.2% at 5 years and 10.4% vs 2.1% at 10 years (hazard ratio, 5.25; P = .004). These findings were held in multivariate models (adjusted sub-hazard ratio [sHR], 5.61; 95% CI, 1.52-20.70) and among women without a pathogenic variant (adjusted sHR, 5.67; 95% CI, 1.54-20.90).
- The researchers also found a low risk for contralateral breast cancer among women without pathogenic variants, which could inform surgical decision-making.
IN PRACTICE:
Although the number of women positive for a germline pathogenic variant was small (n = 33) and “results should be interpreted cautiously,” the analysis signals “the importance of genetic testing” in younger breast cancer survivors to gauge their risk for a second primary breast cancer, the authors concluded. The authors added that their “finding of a higher risk of [second primary breast cancer] among those diagnosed with in situ primary [breast cancer] merits further investigation.”
SOURCE:
This study, led by Kristen D. Brantley, PhD, from Harvard T. H. Chan School of Public Health, Boston, was published online in JAMA Oncology.
LIMITATIONS:
A small number of second breast cancer events limited the authors’ ability to assess the effects of multiple risk factors together. Data on risk factors might be incomplete. About 9% of participants completed abbreviated questionnaires that did not include information on body mass index, alcohol, smoking, and family history. Frequencies of pathogenic variants besides BRCA1 and BRCA2 may be underestimated.
DISCLOSURES:
This study received no external funding. Four authors reported receiving grants or royalties outside this work. Other reported no competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Women who are diagnosed with breast cancer at age 40 or younger are about two to three times more likely to develop second primary breast cancer compared with women who are older when first diagnosed.
- However, data are lacking on whether certain factors increase a woman’s risk for a second primary breast cancer.
- To classify the risk of developing a second primary breast cancer, the researchers evaluated a main cohort of 685 patients with stages 0-III breast cancer who were diagnosed at age 40 years or younger and had undergone unilateral mastectomy or lumpectomy as primary surgery between August 2006 and June 2015. The team also analyzed data on 547 younger women who had a bilateral mastectomy.
- The researchers assessed various breast cancer risk factors, including self-reported ethnicity, race, age, family history of breast or ovarian cancer, germline genetics, tumor stage, grade, and receptor status.
- The primary outcome was the diagnosis of a second primary breast cancer that occurred at least 6 months after the initial diagnosis of primary breast cancer.
TAKEAWAY:
- Among the 685 main study participants, 17 (2.5%) developed a second primary breast cancer (15 contralateral and 2 ipsilateral) over a median of 4.2 years since their primary diagnosis. The 5- and 10-year cumulative incidence of a second primary breast cancer was 1.5% and 2.6%, respectively.
- Overall, only 33 women were positive for a germline pathogenic variant, and having a pathogenic variant was associated with a fourfold higher risk for second primary breast cancer compared with noncarriers at 5 years (5.5% vs 1.3%) and at 10 years (8.9% vs 2.2%). These findings were held in multivariate models.
- Patients initially diagnosed with in situ disease had more than a fivefold higher risk for second primary breast cancer compared with those initially diagnosed with invasive disease — 6.2% vs 1.2% at 5 years and 10.4% vs 2.1% at 10 years (hazard ratio, 5.25; P = .004). These findings were held in multivariate models (adjusted sub-hazard ratio [sHR], 5.61; 95% CI, 1.52-20.70) and among women without a pathogenic variant (adjusted sHR, 5.67; 95% CI, 1.54-20.90).
- The researchers also found a low risk for contralateral breast cancer among women without pathogenic variants, which could inform surgical decision-making.
IN PRACTICE:
Although the number of women positive for a germline pathogenic variant was small (n = 33) and “results should be interpreted cautiously,” the analysis signals “the importance of genetic testing” in younger breast cancer survivors to gauge their risk for a second primary breast cancer, the authors concluded. The authors added that their “finding of a higher risk of [second primary breast cancer] among those diagnosed with in situ primary [breast cancer] merits further investigation.”
SOURCE:
This study, led by Kristen D. Brantley, PhD, from Harvard T. H. Chan School of Public Health, Boston, was published online in JAMA Oncology.
LIMITATIONS:
A small number of second breast cancer events limited the authors’ ability to assess the effects of multiple risk factors together. Data on risk factors might be incomplete. About 9% of participants completed abbreviated questionnaires that did not include information on body mass index, alcohol, smoking, and family history. Frequencies of pathogenic variants besides BRCA1 and BRCA2 may be underestimated.
DISCLOSURES:
This study received no external funding. Four authors reported receiving grants or royalties outside this work. Other reported no competing interests.
A version of this article appeared on Medscape.com.
Most Targeted Cancer Drugs Lack Substantial Clinical Benefit
TOPLINE:
METHODOLOGY:
- The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
- Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
- In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
- The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
- The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).
TAKEAWAY:
- The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
- Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
- Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
- Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.
IN PRACTICE:
“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”
SOURCE:
The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.
LIMITATIONS:
The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.
DISCLOSURES:
The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
- Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
- In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
- The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
- The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).
TAKEAWAY:
- The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
- Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
- Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
- Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.
IN PRACTICE:
“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”
SOURCE:
The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.
LIMITATIONS:
The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.
DISCLOSURES:
The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
- Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
- In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
- The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
- The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).
TAKEAWAY:
- The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
- Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
- Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
- Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.
IN PRACTICE:
“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”
SOURCE:
The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.
LIMITATIONS:
The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.
DISCLOSURES:
The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.
A version of this article appeared on Medscape.com.
Meat Linked to Higher Erectile Dysfunction Risk
Rachel S. Rubin, MD: Welcome to another episode of Sex Matters. I’m Dr. Rachel Rubin. I’m a urologist and sexual medicine specialist based in the Washington, DC area, and I interview amazingly cool people doing research in sexual medicine.
I heard an incredible lecture while I was at the Mayo Clinic urology conference by Dr. Stacy Loeb, who is a wonderful researcher of all things prostate cancer and men’s health, who is now talking more plant-based diets. Her lecture was so good, I begged her to join me for this discussion.
Dr. Loeb, I would love for you to introduce yourself.
Stacy Loeb, MD: I’m Dr. Loeb. I’m a urologist at New York University in the Manhattan VA, and I recently became board certified in lifestyle medicine because it’s so important for sexual health and, really, everything that we do.
Dr. Rubin: You recently became very interested in studying plant-based diets. How did that start, and how has the research evolved over time?
Dr. Loeb: It’s really amazing. For one thing, more of our patients with prostate cancer die of heart disease than of prostate cancer. And erectile dysfunction is really an early warning sign of cardiovascular disease. We felt like it was incumbent upon us, even within urology and sexual medicine, to better understand the basis for lifestyle modification that can help with these issues.
Dr. Rubin: Tell us more about what you found for erectile dysfunction. How much benefit do people get by switching to a plant-based diet?
Dr. Loeb: First we looked at erectile function in men without prostate cancer in the health professionals follow-up study, a very large cohort study out of Harvard University. We found that among omnivorous people, those who ate more plant-based and less animal-based food were less likely to have incident erectile dysfunction. Then, we published a new paper looking at patients with prostate cancer. These men have extra challenges for sexual function because in addition to the standard cardiovascular changes with aging, prostate cancer treatment can affect the nerves that are involved in erections. But amazingly, even in that population, we found that the men who ate more plant-based and less animal-based food had better scores for erectile function.
That was really good news, and it’s a win-win. There is no reason not to counsel our patients to eat more plant-based foods. Meat is not masculine. Meat is associated with a higher risk for erectile dysfunction and is considered carcinogenic. It’s just something that we should try to stay away from.
Dr. Rubin: How do you counsel patients who might not be ready to go fully plant-based? Is a little better than nothing? How do you even start these conversations with people? Do you have any tips for primary care doctors?
Dr. Loeb: Great question. A little bit is very much better than nothing. In fact, in the health professionals follow-up study, we actually looked at quintiles of people who ate the most meat and animal-based foods and the least plant-based foods all the way up to the most plant-based and the least animal-based diets. Along that spectrum, it really does make a big difference. Anywhere that patients can start from is definitely better than nothing.
Simple things such as Meatless Monday or choosing a few days that they will give up animal-based foods will help. For some people, trying new things is easier than cutting things out, for example, trying a milk substitute such as oat, almond, or soy milk instead of dairy milk. That could be a great first step, or trying some dishes that don’t include meat — maybe a tofu stir fry or a taco or burrito without the meat.
There are many great options out there. In terms of resources for doctors, the Physicians Committee for Responsible Medicine has a great website. They have fact sheets for a lot of the common questions that people ask such as how can I get enough protein or calcium on a plant-based diet? This isn’t a problem at all. In fact, Novak Djokovic and many other elite athletes eat plant-based diets, and they get enough protein with a much higher requirement than most of us who are not elite athletes. These fact sheets explain which plant foods are the best
I also like Nutritionfacts.org. They also have all kinds of great videos and resources. Both of these websites have recipes that were created by doctors and nutritionists.
We can suggest that our patients work with a nutritionist or join a virtual program. For example, Plant Powered here in New York has virtual plant-based jumpstart programs. People around the country can get in on programs that have nutritionists and health coaches — for people who want a boost.
Dr. Rubin: The data are really compelling. When you were speaking, not a person in the room was interested in having a steak that night for dinner, even with a steakhouse in the hotel.
What do you say to men who have prostate cancer or suffer from erectile dysfunction? Do any data show that by going plant-based you may show improvements? We have recent studies that show that regular exercise might be as good as Viagra.
Dr. Loeb: It’s definitely not too late, even if you’ve already been diagnosed with these conditions. In my own practice, I have seen changes in patients. In fact, one of the case scenarios that I submitted for the lifestyle medicine boards was a patient who adopted a whole food, plant-based diet and no longer uses Viagra. This is definitely something that’s possible to do with intensive lifestyle modification.
Dr. Rubin: Maybe vegetables are the new sexual health aide. How can people find out more? I know you have a Sirius XM radio show.
Dr. Loeb: It’s the Men’s Health Show on Sirius XM channel 110. It’s on Wednesdays from 6:00 to 8:00 PM ET, or you can listen to it on demand anytime through the Sirius XM app.
Dr. Rubin: You have done an enormous amount of research in prostate cancer and sexual medicine. You are an all-star in the field. Thank you for sharing all of your knowledge about plant-based diets. You’ve given us all a lot to think about today.
Dr. Rubin has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, and Endo.
A version of this article appeared on Medscape.com.
Rachel S. Rubin, MD: Welcome to another episode of Sex Matters. I’m Dr. Rachel Rubin. I’m a urologist and sexual medicine specialist based in the Washington, DC area, and I interview amazingly cool people doing research in sexual medicine.
I heard an incredible lecture while I was at the Mayo Clinic urology conference by Dr. Stacy Loeb, who is a wonderful researcher of all things prostate cancer and men’s health, who is now talking more plant-based diets. Her lecture was so good, I begged her to join me for this discussion.
Dr. Loeb, I would love for you to introduce yourself.
Stacy Loeb, MD: I’m Dr. Loeb. I’m a urologist at New York University in the Manhattan VA, and I recently became board certified in lifestyle medicine because it’s so important for sexual health and, really, everything that we do.
Dr. Rubin: You recently became very interested in studying plant-based diets. How did that start, and how has the research evolved over time?
Dr. Loeb: It’s really amazing. For one thing, more of our patients with prostate cancer die of heart disease than of prostate cancer. And erectile dysfunction is really an early warning sign of cardiovascular disease. We felt like it was incumbent upon us, even within urology and sexual medicine, to better understand the basis for lifestyle modification that can help with these issues.
Dr. Rubin: Tell us more about what you found for erectile dysfunction. How much benefit do people get by switching to a plant-based diet?
Dr. Loeb: First we looked at erectile function in men without prostate cancer in the health professionals follow-up study, a very large cohort study out of Harvard University. We found that among omnivorous people, those who ate more plant-based and less animal-based food were less likely to have incident erectile dysfunction. Then, we published a new paper looking at patients with prostate cancer. These men have extra challenges for sexual function because in addition to the standard cardiovascular changes with aging, prostate cancer treatment can affect the nerves that are involved in erections. But amazingly, even in that population, we found that the men who ate more plant-based and less animal-based food had better scores for erectile function.
That was really good news, and it’s a win-win. There is no reason not to counsel our patients to eat more plant-based foods. Meat is not masculine. Meat is associated with a higher risk for erectile dysfunction and is considered carcinogenic. It’s just something that we should try to stay away from.
Dr. Rubin: How do you counsel patients who might not be ready to go fully plant-based? Is a little better than nothing? How do you even start these conversations with people? Do you have any tips for primary care doctors?
Dr. Loeb: Great question. A little bit is very much better than nothing. In fact, in the health professionals follow-up study, we actually looked at quintiles of people who ate the most meat and animal-based foods and the least plant-based foods all the way up to the most plant-based and the least animal-based diets. Along that spectrum, it really does make a big difference. Anywhere that patients can start from is definitely better than nothing.
Simple things such as Meatless Monday or choosing a few days that they will give up animal-based foods will help. For some people, trying new things is easier than cutting things out, for example, trying a milk substitute such as oat, almond, or soy milk instead of dairy milk. That could be a great first step, or trying some dishes that don’t include meat — maybe a tofu stir fry or a taco or burrito without the meat.
There are many great options out there. In terms of resources for doctors, the Physicians Committee for Responsible Medicine has a great website. They have fact sheets for a lot of the common questions that people ask such as how can I get enough protein or calcium on a plant-based diet? This isn’t a problem at all. In fact, Novak Djokovic and many other elite athletes eat plant-based diets, and they get enough protein with a much higher requirement than most of us who are not elite athletes. These fact sheets explain which plant foods are the best
I also like Nutritionfacts.org. They also have all kinds of great videos and resources. Both of these websites have recipes that were created by doctors and nutritionists.
We can suggest that our patients work with a nutritionist or join a virtual program. For example, Plant Powered here in New York has virtual plant-based jumpstart programs. People around the country can get in on programs that have nutritionists and health coaches — for people who want a boost.
Dr. Rubin: The data are really compelling. When you were speaking, not a person in the room was interested in having a steak that night for dinner, even with a steakhouse in the hotel.
What do you say to men who have prostate cancer or suffer from erectile dysfunction? Do any data show that by going plant-based you may show improvements? We have recent studies that show that regular exercise might be as good as Viagra.
Dr. Loeb: It’s definitely not too late, even if you’ve already been diagnosed with these conditions. In my own practice, I have seen changes in patients. In fact, one of the case scenarios that I submitted for the lifestyle medicine boards was a patient who adopted a whole food, plant-based diet and no longer uses Viagra. This is definitely something that’s possible to do with intensive lifestyle modification.
Dr. Rubin: Maybe vegetables are the new sexual health aide. How can people find out more? I know you have a Sirius XM radio show.
Dr. Loeb: It’s the Men’s Health Show on Sirius XM channel 110. It’s on Wednesdays from 6:00 to 8:00 PM ET, or you can listen to it on demand anytime through the Sirius XM app.
Dr. Rubin: You have done an enormous amount of research in prostate cancer and sexual medicine. You are an all-star in the field. Thank you for sharing all of your knowledge about plant-based diets. You’ve given us all a lot to think about today.
Dr. Rubin has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, and Endo.
A version of this article appeared on Medscape.com.
Rachel S. Rubin, MD: Welcome to another episode of Sex Matters. I’m Dr. Rachel Rubin. I’m a urologist and sexual medicine specialist based in the Washington, DC area, and I interview amazingly cool people doing research in sexual medicine.
I heard an incredible lecture while I was at the Mayo Clinic urology conference by Dr. Stacy Loeb, who is a wonderful researcher of all things prostate cancer and men’s health, who is now talking more plant-based diets. Her lecture was so good, I begged her to join me for this discussion.
Dr. Loeb, I would love for you to introduce yourself.
Stacy Loeb, MD: I’m Dr. Loeb. I’m a urologist at New York University in the Manhattan VA, and I recently became board certified in lifestyle medicine because it’s so important for sexual health and, really, everything that we do.
Dr. Rubin: You recently became very interested in studying plant-based diets. How did that start, and how has the research evolved over time?
Dr. Loeb: It’s really amazing. For one thing, more of our patients with prostate cancer die of heart disease than of prostate cancer. And erectile dysfunction is really an early warning sign of cardiovascular disease. We felt like it was incumbent upon us, even within urology and sexual medicine, to better understand the basis for lifestyle modification that can help with these issues.
Dr. Rubin: Tell us more about what you found for erectile dysfunction. How much benefit do people get by switching to a plant-based diet?
Dr. Loeb: First we looked at erectile function in men without prostate cancer in the health professionals follow-up study, a very large cohort study out of Harvard University. We found that among omnivorous people, those who ate more plant-based and less animal-based food were less likely to have incident erectile dysfunction. Then, we published a new paper looking at patients with prostate cancer. These men have extra challenges for sexual function because in addition to the standard cardiovascular changes with aging, prostate cancer treatment can affect the nerves that are involved in erections. But amazingly, even in that population, we found that the men who ate more plant-based and less animal-based food had better scores for erectile function.
That was really good news, and it’s a win-win. There is no reason not to counsel our patients to eat more plant-based foods. Meat is not masculine. Meat is associated with a higher risk for erectile dysfunction and is considered carcinogenic. It’s just something that we should try to stay away from.
Dr. Rubin: How do you counsel patients who might not be ready to go fully plant-based? Is a little better than nothing? How do you even start these conversations with people? Do you have any tips for primary care doctors?
Dr. Loeb: Great question. A little bit is very much better than nothing. In fact, in the health professionals follow-up study, we actually looked at quintiles of people who ate the most meat and animal-based foods and the least plant-based foods all the way up to the most plant-based and the least animal-based diets. Along that spectrum, it really does make a big difference. Anywhere that patients can start from is definitely better than nothing.
Simple things such as Meatless Monday or choosing a few days that they will give up animal-based foods will help. For some people, trying new things is easier than cutting things out, for example, trying a milk substitute such as oat, almond, or soy milk instead of dairy milk. That could be a great first step, or trying some dishes that don’t include meat — maybe a tofu stir fry or a taco or burrito without the meat.
There are many great options out there. In terms of resources for doctors, the Physicians Committee for Responsible Medicine has a great website. They have fact sheets for a lot of the common questions that people ask such as how can I get enough protein or calcium on a plant-based diet? This isn’t a problem at all. In fact, Novak Djokovic and many other elite athletes eat plant-based diets, and they get enough protein with a much higher requirement than most of us who are not elite athletes. These fact sheets explain which plant foods are the best
I also like Nutritionfacts.org. They also have all kinds of great videos and resources. Both of these websites have recipes that were created by doctors and nutritionists.
We can suggest that our patients work with a nutritionist or join a virtual program. For example, Plant Powered here in New York has virtual plant-based jumpstart programs. People around the country can get in on programs that have nutritionists and health coaches — for people who want a boost.
Dr. Rubin: The data are really compelling. When you were speaking, not a person in the room was interested in having a steak that night for dinner, even with a steakhouse in the hotel.
What do you say to men who have prostate cancer or suffer from erectile dysfunction? Do any data show that by going plant-based you may show improvements? We have recent studies that show that regular exercise might be as good as Viagra.
Dr. Loeb: It’s definitely not too late, even if you’ve already been diagnosed with these conditions. In my own practice, I have seen changes in patients. In fact, one of the case scenarios that I submitted for the lifestyle medicine boards was a patient who adopted a whole food, plant-based diet and no longer uses Viagra. This is definitely something that’s possible to do with intensive lifestyle modification.
Dr. Rubin: Maybe vegetables are the new sexual health aide. How can people find out more? I know you have a Sirius XM radio show.
Dr. Loeb: It’s the Men’s Health Show on Sirius XM channel 110. It’s on Wednesdays from 6:00 to 8:00 PM ET, or you can listen to it on demand anytime through the Sirius XM app.
Dr. Rubin: You have done an enormous amount of research in prostate cancer and sexual medicine. You are an all-star in the field. Thank you for sharing all of your knowledge about plant-based diets. You’ve given us all a lot to think about today.
Dr. Rubin has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, and Endo.
A version of this article appeared on Medscape.com.
Blood Test Shows Promise for Improving CRC Screening
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
How New ICI Combos Change Bladder Cancer Management
according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.
Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
What's New in The Updated Guidelines?
Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.
This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.
“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.
“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.
Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
Other Current Strategies for Localized Bladder Cancer Management
The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.
Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.
The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.
Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.
What are the New Options for Treating Metastatic Urothelial Bladder Cancer?
The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).
Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.
A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
What Do the Latest Studies of Combination Therapy Show?
Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.
A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).
Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.
Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.
In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
What About Targeted Therapy?
Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.
“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.
Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.
according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.
Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
What's New in The Updated Guidelines?
Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.
This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.
“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.
“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.
Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
Other Current Strategies for Localized Bladder Cancer Management
The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.
Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.
The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.
Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.
What are the New Options for Treating Metastatic Urothelial Bladder Cancer?
The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).
Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.
A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
What Do the Latest Studies of Combination Therapy Show?
Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.
A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).
Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.
Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.
In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
What About Targeted Therapy?
Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.
“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.
Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.
according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.
Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
What's New in The Updated Guidelines?
Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.
This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.
“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.
“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.
Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
Other Current Strategies for Localized Bladder Cancer Management
The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.
Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.
The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.
Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.
What are the New Options for Treating Metastatic Urothelial Bladder Cancer?
The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).
Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.
A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
What Do the Latest Studies of Combination Therapy Show?
Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.
A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).
Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.
Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.
In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
What About Targeted Therapy?
Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.
“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.
Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.
FROM NCCN 2024
Panel: MRD Tests May Speed Myeloma Tx Approvals
The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?
The FDA is not bound to accept the recommendations of its panels, but often does so.
ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.
There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).
“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”
“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.
Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.
The April 12 meeting was somewhat unusual for ODAC.
Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.
These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.
In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.
The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.
The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.
The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.
In the briefing document for the meeting, the FDA also emphasized the need for new treatments.
Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.
The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.
Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.
“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”
Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.
“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”
The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?
The FDA is not bound to accept the recommendations of its panels, but often does so.
ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.
There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).
“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”
“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.
Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.
The April 12 meeting was somewhat unusual for ODAC.
Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.
These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.
In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.
The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.
The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.
The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.
In the briefing document for the meeting, the FDA also emphasized the need for new treatments.
Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.
The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.
Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.
“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”
Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.
“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”
The Oncologic Drugs Advisory Committee (ODAC) of the US Food and Drug Administration (FDA) voted 12-0 on April 12 on the following question: Does the evidence support the use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials?
The FDA is not bound to accept the recommendations of its panels, but often does so.
ODAC panelists said they felt comfortable in this recommendation because they expected the FDA to mandate confirmatory studies of any drugs to be given accelerated approval based on MRD data.
There’s a risk that MRD results might mislead regulators into clearing a drug later found to lack benefit, said Christopher Hourigan, DM, DPhil, an ODAC panelist and a physician-scientist at Virginia Tech, Blacksburg, Virginia, who treats people with blood cancer. Further tests would ultimately show if drugs cleared based on MRD data actually delivered benefits such as extending progression-free survival (PFS).
“That’s why we’re talking about accelerated approval,” Dr. Hourigan said. “There is harm to inaction. We’re not currently curing people in multiple myeloma. I’m not willing to make patients wait on principle for a theoretical perfect that may never come.”
“Our responsibility is to accept the world as messy and be agile enough to adapt and iterate that the evidence develops rather than create barriers to the work of discovering effective new therapies for these patients,” he added.
Advances in testing now allow for detection of the presence of malignant cells at orders of magnitude below previous assessments. MRD assays used in tracking what’s happening with myeloma generally have a sensitivity level of 10-5, or a detection capacity of one cell of 100,000, said Ola Landgren, MD, PhD, of the University of Miami, Miami, Florida, during a presentation at the meeting.
The April 12 meeting was somewhat unusual for ODAC.
Instead of reviewing the benefits and risks of a specific drug, the panel reviewed results from two separate major research efforts done to see how MRD could be used in development of drugs.
These were Dr. Landgren’s EVIDENCE (Evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma) meta-analysis, and the similar work of the i2TEAMM group, affiliated with the International Myeloma Foundation.
In its review, the FDA staff noted differences in the approaches of the two groups. In its analysis, the i2TEAMM removed information about patients with missing MRD data, while the University of Miami team retained information about these kinds of patients in the analyses and assigned their status to be MRD positive.
The FDA staff also noted in their review and presentations weaknesses in the case for MRD. For example, the FDA staff noted that the treatment effect on MRD negativity was not statistically significant in 4 of the 8 treatment comparisons in the work from Dr. Landgren and colleagues.
The FDA staff looked at what these analyses suggested at both an individual level and trial level. The data from these two research projects taken as a whole showed “strong individual-level” associations between negative MRD findings and later positive outcomes for patients, although trial-level associations were “weak to moderate” in some cases, the staff wrote.
The FDA staff concluded that the research appeared to support arguments in favor of the “prognostic value,” even with outstanding questions about how best to use this test.
In the briefing document for the meeting, the FDA also emphasized the need for new treatments.
Multiple myeloma remains an incurable disease with a 5-year relative survival rate of 59.8%, even after significant recent progress in treatment, the agency said. In the past decade, the FDA has approved 15 new drugs and greater than 20 new indications have been approved for the treatment of patients with multiple myeloma.
The FDA has been working with drugmakers and academic researchers for several years to address the potential of MRD in development of blood cancers. The agency in 2020 issued a guidance document on this issue.
Several ODAC members praised the i2TEAMM and Dr. Landgren’s EVIDENCE teams for their work, which took place across several nations and extended over many years.
“This was a herculean effort. It really changes the playbook for how we think about biomarkers across all cancer types,” said ODAC panelist Neil Vasan, MD, PhD, of Columbia University, New York, NY. “To me, the important word was reasonable. Is this a reasonable surrogate endpoint? Is this a reasonable intermediate endpoint? I think it is more than reasonable.”
Still, ODAC panelist Jorge Nieva, MD, raised a point of concern about how use of MRD as an endpoint could change the design of studies. He urged caution among researchers about potential ramping up of collection of MRD tests in search of more robust data, which could lead to more testing for patients.
“I have this tremendous fear that this is going to mean every myeloma protocol has a marrow biopsy every six weeks on the patients forever,” said Dr. Nieva of the Keck School of Medicine, University of Southern California, Los Angeles. “I just don’t want to see that happen. So I think we need to balance these two things.”