User login
Getting cancer research on track again may require a ‘behemoth’ effort
In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, to get cancer research just back up to pre-COVID-19 pandemic levels.
There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.
Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.
Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.
“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.
Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.
“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
Can cancer be cured?
The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.
Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.
“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.
But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.
“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”
Closing the loop on data sharing
Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.
“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.
Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.
“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.
Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
A shift in funding priorities?
Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.
“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.
But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.
“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
The pandemic stymies cancer research
The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.
“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”
But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”
In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, to get cancer research just back up to pre-COVID-19 pandemic levels.
There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.
Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.
Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.
“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.
Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.
“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
Can cancer be cured?
The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.
Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.
“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.
But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.
“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”
Closing the loop on data sharing
Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.
“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.
Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.
“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.
Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
A shift in funding priorities?
Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.
“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.
But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.
“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
The pandemic stymies cancer research
The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.
“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”
But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”
In 2016, as vice president, Joe Biden launched the Cancer Moonshot program just 1 year after his son Beau died from glioblastoma multiforme. His objective, he said, was to “cure” cancer, but to get close to that goal, to get cancer research just back up to pre-COVID-19 pandemic levels.
There has been a significant decrease in the launch of new clinical trials for cancer and biologic therapies since 2020. “That can affect every aspect of our research operation. It really affected our capacity to continue to move forward at a fast pace. It will require a behemoth effort to get back to pre-COVID times,” said Tanios S. Bekaii-Saab, MD, leader of the gastrointestinal cancer program at Mayo Clinic in Phoenix.
Congress passed the 21st Century Cures Act in 2016 authorizing $1.8 billion for Cancer Moonshot over 7 years. More recently, the program received $194 million from the $6.9 billion National Cancer Institute budget in FY 2022.
Joseph Alvarnas, MD, a hematologist oncologist and vice president of government affairs at City of Hope, Duarte, Calif., sees the Moonshot budget as a potential shortcoming.
“The priorities are well founded and based on what we would think are the most important things to cover, but, if we’re going to achieve these extraordinarily ambitious goals of halving cancer mortality and serving communities more equitably, it’s going to need more funding positioned at making these things real,” he said.
Moonshot is being positioned as an opportunity to double down on efforts started in 2016, but treating cancer is complex and goes well beyond funding new research.
“We know that we have amazing research and progress around innovations that will drive us toward the goal of reducing the death rate from cancer. But we also know that we have tools that aren’t reaching all parts of the country, so we have a great opportunity to make sure that we’re doing all we can to prevent, detect and treat cancer,” Dr. Carnival said.
Can cancer be cured?
The Biden administration relaunched Moonshot in 2022 with newly defined goals: Cut the rate of cancer-related deaths in half within 25 years; improve the experience of people with cancer, cancer survivors, and their families; and “end cancer as we know it,” President Biden said in a press conference in February.
Cancer is the second leading cause of death in the United States after heart disease, but it may indeed be possible to cut the total number of cancer-related deaths in half over the next 25 years.
“As a hematologist who’s been involved in both research and clinical care, I think it’s important to realize this is actually doable. Between 1990 and 2020 cancer mortality rates decreased by 31%, and in the last American Cancer Society’s annual report, mortality rates dropped by the largest percentages for 2 consecutive years in a row. The question shifts now from ‘Is this possible? to ‘How do we ensure that it’s possible?’ The spirit of Cancer Moonshot 2.0 is identifying the multiple paths to move this effort forward,” Dr. Alvarnas said.
But without a significant infusion of cash for research, it’s doubtful cancer-related deaths will drop by 50% over the next 25 years.
“There are a lot of big and lofty goals in Cancer Moonshot, and the words ‘ending cancer,’ well those are big words,” Dr. Bekaii-Saab said. “The reality is how do we measure in 25 years the impact of this today? I think it will require significantly more funding over the next few years to achieve the goals set by the Moonshot. Otherwise it will be a 7-year done deal that will accrue a lot of great numbers but won’t make a dent in those goals for the next 25 years. To stop it at some point and not invest more into it, we will probably lose most of the benefit.”
Closing the loop on data sharing
Moonshot has been instrumental in fostering research collaborations by encouraging data sharing among scientists.
“It also brought together a new way for the National Cancer Institute and Department of Energy to drive progress on some of the big data initiatives. The initial Cancer Moonshot infused a sense of urgency and hope into this effort,” said Danielle Carnival, PhD, coordinator of Cancer Moonshot.
Between 2017 and 2022, Cancer Moonshot created more than 70 consortiums or programs, and funded about 240 research projects. Its fundamental goals of improving data sharing and encouraging collaboration are very important, Dr. Bekaii-Saab said.
“Because, historically, what happens with cancer is that researchers compete for resources...and they become very protective of their data. Sharing gets more difficult, collaborations become more onerous, and it becomes counterproductive,” he said.
Dr. Bekaii-Saab highlighted two networks created specifically for data sharing. They include the Human Tumor Atlas for cellular, morphological, and molecular tumor data, and PDXNet, a patient derived xenograft research network.
A shift in funding priorities?
Cancer funding has been stagnant for years. When adjusted for growth, it hasn’t had a significant infusion of funding since at least 2003—at least in relative terms, Dr. Bekaii-Saab said. “This affects a lot of the things we do, including NCI-funded clinical trials. It pushes us to work with the private sector, which is not necessarily a detriment, but it doesn’t advance the academic mission at the same level. So, overall, I wouldn’t call it tragic, but I do think we’re falling behind,” he said.
“I think when we do the process for the budget for FY24 and after we’ve had time to really explore the best ideas and build the foundation for some of these new aspects of the Cancer Moonshot, we hope to have something more concrete going toward these efforts,” Dr. Carnival said.
But in addition to funding, Dr. Alvarnas says, it is equally important to address gaps in care. Not all patients have access to existing cancer treatments.
“The great challenge to us in the 2020s is not only about developing new and more effective technologies, but also in doing a better job of getting existing life-saving treatments into the hands of underserved populations. One of the really positive challenges set forth by the Biden administration is the idea that financing care equity is as important, if not more so, than advancing technologies. If there’s been stagnation, it’s because from a government and resourcing point of view, that priority has been ineffectively supported financially.”
The pandemic stymies cancer research
The pandemic has had a significant impact on cancer research. As in other fields, it disrupted ongoing research, but it may have also contributed to the loss of employees who resigned in what’s been called the “Great Resignation.” “A lot of employees just decided to change jobs in the middle of the pandemic, which led to a cancer research staffing crisis,” Dr. Bekaii-Saab said.
“We all recognized that turning so much of the attention of the entire biomedical research engine and health system to the COVID-19 pandemic would have an impact across cancer research, screenings and care,” Dr. Carnival said. “There is work to do to get us back to whole, but from a research perspective, we’ve seen a reorientation of the trial networks we were using for COVID-19 research, back to their initial purpose. Some of those are cancer and oncology networks, so we’re excited about that and fully believe that we can catch up.”
But then there’s also the impact the pandemic has had on cancer patients who delayed their care at the primary level. This, Dr. Bekaii-Saab fears, will lead to more patients presenting with more advanced disease in years to come. “One of the biggest problems was that a lot of patients delayed their care at the primary level. My biggest concern is that in the years to come we will see a lot more patients presenting with more advanced cancer.”
Genomic Assays in HR-Positive/HER2-Negative Breast Cancer
As both a clinician and investigator in the breast cancer space, how would you describe our current understanding of genomic assays in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease?
Dr. Kalinsky: There are a number of commercially-available assays for patients with early-stage HR-positive/HER2-negative breast cancer. We have seen the results of 3 large randomized phase 3 trials that have demonstrated and helped establish the clinical utility of assays, including the oncotype DX 21-gene recurrence score. This was evaluated in patients with node-negative breast cancer in the TAILORx trial and in patients with 1 to 3 nodes involved in the RxPONDER trial.
We also have data with the 70-gene MammaPrint assay from the MINDACT study, looking for patients who had a discordance between clinical and genomic risk. MINDACT has been published and was updated recently with data for 8-year distant metastasis-free survival. It is these studies that have helped establish what we do in the clinic and when we consider offering genomic assays in patients with this subtype of breast cancer.
How are you working to bring these genomic assays into practice?
Dr. Kalinsky: In 2020, we reported the initial results from the RxPonder study demonstrating that for patients with HR-positive HER2-negative breast cancer with 1 to 3 nodes involved, two-thirds of the patients were postmenopausal. For patients who had a recurrence score of 25 or less, we did not identify a subgroup of patients who benefited from chemotherapy.
For the premenopausal women, which was one-third of the patients, we saw that all those patients benefited from the addition of chemotherapy if the recurrence score was 25 or less. We did a number of subgroup analyses, which we reported on at the San Antonio Breast Cancer Symposium in 2021.
Several analyses are ongoing. These include some subgroup analyses looking at quality of life as well as a collection of circulating markers. In addition, there is ongoing biomarker work looking at tumor tissue to see if there are differences between the biology of premenopausal versus postmenopausal women.
What value does genomic testing bring to the treatment of HR-positive/HER2-negative breast cancer?
Dr. Kalinsky: These assays have achieved clinical utility, and this has been reflected in the recent update to the ASCO Guidelines for genomic assays. We have also learned that it is not just the assay by itself, but also the clinical features of a patient that help determine risk. In other words, it’s not just dependent on the score, but also involves the context of other important clinical features, including patient and tumor characteristics such as tumor size, patient age, and tumor grade. All of these add value and help us assess a patient’s individualized risk.
Is there a specific profile or qualifications candidates must meet for genomic testing to be done?
Dr. Kalinsky: We offer genomic tests for patients with HR-positive/HER2-negative breast cancer who are node-negative or have 1 to 3 nodes involved. There are other commercially-available tests such as the Breast Cancer Index, which assesses risk of recurrence in years 5 to 10 and looks at whether there is potential utility for continuing anti-estrogen therapy. That assay provides both prognostic and predictive information.
Is there any additional insight on genomic assays in HR-positive/HER2-negative breast cancer you would like to share?
Dr. Kalinsky: We’ve been talking about tumor-based assays. However, the question is, what’s going to be the role for circulating markers, such as circulating tumor DNA (ctDNA) or circulating tumor cells? There is a lot of information that we’re hoping to understand, not just regarding the prognostic significance but also the predictive utility. If you have a patient with a subtype of breast cancer and we know this subgroup can be at risk for late recurrence, if you identify said marker and you switch the therapy, do you see clearance of ctDNA? Does that lead to an improvement in outcome? That is an important question that is going to be answered in current and future trials.
As both a clinician and investigator in the breast cancer space, how would you describe our current understanding of genomic assays in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease?
Dr. Kalinsky: There are a number of commercially-available assays for patients with early-stage HR-positive/HER2-negative breast cancer. We have seen the results of 3 large randomized phase 3 trials that have demonstrated and helped establish the clinical utility of assays, including the oncotype DX 21-gene recurrence score. This was evaluated in patients with node-negative breast cancer in the TAILORx trial and in patients with 1 to 3 nodes involved in the RxPONDER trial.
We also have data with the 70-gene MammaPrint assay from the MINDACT study, looking for patients who had a discordance between clinical and genomic risk. MINDACT has been published and was updated recently with data for 8-year distant metastasis-free survival. It is these studies that have helped establish what we do in the clinic and when we consider offering genomic assays in patients with this subtype of breast cancer.
How are you working to bring these genomic assays into practice?
Dr. Kalinsky: In 2020, we reported the initial results from the RxPonder study demonstrating that for patients with HR-positive HER2-negative breast cancer with 1 to 3 nodes involved, two-thirds of the patients were postmenopausal. For patients who had a recurrence score of 25 or less, we did not identify a subgroup of patients who benefited from chemotherapy.
For the premenopausal women, which was one-third of the patients, we saw that all those patients benefited from the addition of chemotherapy if the recurrence score was 25 or less. We did a number of subgroup analyses, which we reported on at the San Antonio Breast Cancer Symposium in 2021.
Several analyses are ongoing. These include some subgroup analyses looking at quality of life as well as a collection of circulating markers. In addition, there is ongoing biomarker work looking at tumor tissue to see if there are differences between the biology of premenopausal versus postmenopausal women.
What value does genomic testing bring to the treatment of HR-positive/HER2-negative breast cancer?
Dr. Kalinsky: These assays have achieved clinical utility, and this has been reflected in the recent update to the ASCO Guidelines for genomic assays. We have also learned that it is not just the assay by itself, but also the clinical features of a patient that help determine risk. In other words, it’s not just dependent on the score, but also involves the context of other important clinical features, including patient and tumor characteristics such as tumor size, patient age, and tumor grade. All of these add value and help us assess a patient’s individualized risk.
Is there a specific profile or qualifications candidates must meet for genomic testing to be done?
Dr. Kalinsky: We offer genomic tests for patients with HR-positive/HER2-negative breast cancer who are node-negative or have 1 to 3 nodes involved. There are other commercially-available tests such as the Breast Cancer Index, which assesses risk of recurrence in years 5 to 10 and looks at whether there is potential utility for continuing anti-estrogen therapy. That assay provides both prognostic and predictive information.
Is there any additional insight on genomic assays in HR-positive/HER2-negative breast cancer you would like to share?
Dr. Kalinsky: We’ve been talking about tumor-based assays. However, the question is, what’s going to be the role for circulating markers, such as circulating tumor DNA (ctDNA) or circulating tumor cells? There is a lot of information that we’re hoping to understand, not just regarding the prognostic significance but also the predictive utility. If you have a patient with a subtype of breast cancer and we know this subgroup can be at risk for late recurrence, if you identify said marker and you switch the therapy, do you see clearance of ctDNA? Does that lead to an improvement in outcome? That is an important question that is going to be answered in current and future trials.
As both a clinician and investigator in the breast cancer space, how would you describe our current understanding of genomic assays in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease?
Dr. Kalinsky: There are a number of commercially-available assays for patients with early-stage HR-positive/HER2-negative breast cancer. We have seen the results of 3 large randomized phase 3 trials that have demonstrated and helped establish the clinical utility of assays, including the oncotype DX 21-gene recurrence score. This was evaluated in patients with node-negative breast cancer in the TAILORx trial and in patients with 1 to 3 nodes involved in the RxPONDER trial.
We also have data with the 70-gene MammaPrint assay from the MINDACT study, looking for patients who had a discordance between clinical and genomic risk. MINDACT has been published and was updated recently with data for 8-year distant metastasis-free survival. It is these studies that have helped establish what we do in the clinic and when we consider offering genomic assays in patients with this subtype of breast cancer.
How are you working to bring these genomic assays into practice?
Dr. Kalinsky: In 2020, we reported the initial results from the RxPonder study demonstrating that for patients with HR-positive HER2-negative breast cancer with 1 to 3 nodes involved, two-thirds of the patients were postmenopausal. For patients who had a recurrence score of 25 or less, we did not identify a subgroup of patients who benefited from chemotherapy.
For the premenopausal women, which was one-third of the patients, we saw that all those patients benefited from the addition of chemotherapy if the recurrence score was 25 or less. We did a number of subgroup analyses, which we reported on at the San Antonio Breast Cancer Symposium in 2021.
Several analyses are ongoing. These include some subgroup analyses looking at quality of life as well as a collection of circulating markers. In addition, there is ongoing biomarker work looking at tumor tissue to see if there are differences between the biology of premenopausal versus postmenopausal women.
What value does genomic testing bring to the treatment of HR-positive/HER2-negative breast cancer?
Dr. Kalinsky: These assays have achieved clinical utility, and this has been reflected in the recent update to the ASCO Guidelines for genomic assays. We have also learned that it is not just the assay by itself, but also the clinical features of a patient that help determine risk. In other words, it’s not just dependent on the score, but also involves the context of other important clinical features, including patient and tumor characteristics such as tumor size, patient age, and tumor grade. All of these add value and help us assess a patient’s individualized risk.
Is there a specific profile or qualifications candidates must meet for genomic testing to be done?
Dr. Kalinsky: We offer genomic tests for patients with HR-positive/HER2-negative breast cancer who are node-negative or have 1 to 3 nodes involved. There are other commercially-available tests such as the Breast Cancer Index, which assesses risk of recurrence in years 5 to 10 and looks at whether there is potential utility for continuing anti-estrogen therapy. That assay provides both prognostic and predictive information.
Is there any additional insight on genomic assays in HR-positive/HER2-negative breast cancer you would like to share?
Dr. Kalinsky: We’ve been talking about tumor-based assays. However, the question is, what’s going to be the role for circulating markers, such as circulating tumor DNA (ctDNA) or circulating tumor cells? There is a lot of information that we’re hoping to understand, not just regarding the prognostic significance but also the predictive utility. If you have a patient with a subtype of breast cancer and we know this subgroup can be at risk for late recurrence, if you identify said marker and you switch the therapy, do you see clearance of ctDNA? Does that lead to an improvement in outcome? That is an important question that is going to be answered in current and future trials.
Genetic counseling for cancer often costs patients nothing
But even among those who do, the cost is $16 or less, a cohort study shows.
“The findings highlight the relatively low financial costs of genetic counseling, a form of care with potentially substantial implications for cancer treatment,” lead author Mya Roberson, PhD, Vanderbilt University, Nashville, Tenn., and colleagues explained.
The study was published online in JAMA Health Forum.
Genetic counseling is an important feature of cancer care that can affect treatment decisions and surveillance. But coverage of genetic counseling services varies across insurance types.
To understand the costs to patients, the investigators used data from IBM Watson Health MarketScan to create a cohort of privately insured patients with breast, prostate, endometrial, ovarian, colorectal, and pancreatic cancer who had at least one genetic counseling session from 2013 to the end of 2019.
Dr. Roberson and colleagues then calculated out-of-pocket costs – including coinsurance, copayments, and deductibles – and total costs paid on claims for genetic counseling encounters. The cohort included 16,791 patients, the majority of whom had breast cancer.
Although the median insurance payment for genetic counseling encounters was $118 ($58-$211), most patients paid nothing out of pocket for these services. Among the 31% of patients with an out-of-pocket expense, the cost was $16 or less.
Compared with breast cancer patients, men with prostate cancer were 28% more likely to have out-of-pocket costs for genetic counseling, which may “reflect a lack of awareness about the medical necessity of genetic counseling,” the authors suggested.
Overall, the study highlights the value of genetic counseling in cancer care.
“Cancer genetic counseling not only promotes informed decision-making about genetic testing and cancer treatment in the era of precision medicine, but it also is a form of low-cost, high-value care,” the authors wrote.
The study was funded by a grant from the National Cancer Institute. Dr. Roberson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
But even among those who do, the cost is $16 or less, a cohort study shows.
“The findings highlight the relatively low financial costs of genetic counseling, a form of care with potentially substantial implications for cancer treatment,” lead author Mya Roberson, PhD, Vanderbilt University, Nashville, Tenn., and colleagues explained.
The study was published online in JAMA Health Forum.
Genetic counseling is an important feature of cancer care that can affect treatment decisions and surveillance. But coverage of genetic counseling services varies across insurance types.
To understand the costs to patients, the investigators used data from IBM Watson Health MarketScan to create a cohort of privately insured patients with breast, prostate, endometrial, ovarian, colorectal, and pancreatic cancer who had at least one genetic counseling session from 2013 to the end of 2019.
Dr. Roberson and colleagues then calculated out-of-pocket costs – including coinsurance, copayments, and deductibles – and total costs paid on claims for genetic counseling encounters. The cohort included 16,791 patients, the majority of whom had breast cancer.
Although the median insurance payment for genetic counseling encounters was $118 ($58-$211), most patients paid nothing out of pocket for these services. Among the 31% of patients with an out-of-pocket expense, the cost was $16 or less.
Compared with breast cancer patients, men with prostate cancer were 28% more likely to have out-of-pocket costs for genetic counseling, which may “reflect a lack of awareness about the medical necessity of genetic counseling,” the authors suggested.
Overall, the study highlights the value of genetic counseling in cancer care.
“Cancer genetic counseling not only promotes informed decision-making about genetic testing and cancer treatment in the era of precision medicine, but it also is a form of low-cost, high-value care,” the authors wrote.
The study was funded by a grant from the National Cancer Institute. Dr. Roberson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
But even among those who do, the cost is $16 or less, a cohort study shows.
“The findings highlight the relatively low financial costs of genetic counseling, a form of care with potentially substantial implications for cancer treatment,” lead author Mya Roberson, PhD, Vanderbilt University, Nashville, Tenn., and colleagues explained.
The study was published online in JAMA Health Forum.
Genetic counseling is an important feature of cancer care that can affect treatment decisions and surveillance. But coverage of genetic counseling services varies across insurance types.
To understand the costs to patients, the investigators used data from IBM Watson Health MarketScan to create a cohort of privately insured patients with breast, prostate, endometrial, ovarian, colorectal, and pancreatic cancer who had at least one genetic counseling session from 2013 to the end of 2019.
Dr. Roberson and colleagues then calculated out-of-pocket costs – including coinsurance, copayments, and deductibles – and total costs paid on claims for genetic counseling encounters. The cohort included 16,791 patients, the majority of whom had breast cancer.
Although the median insurance payment for genetic counseling encounters was $118 ($58-$211), most patients paid nothing out of pocket for these services. Among the 31% of patients with an out-of-pocket expense, the cost was $16 or less.
Compared with breast cancer patients, men with prostate cancer were 28% more likely to have out-of-pocket costs for genetic counseling, which may “reflect a lack of awareness about the medical necessity of genetic counseling,” the authors suggested.
Overall, the study highlights the value of genetic counseling in cancer care.
“Cancer genetic counseling not only promotes informed decision-making about genetic testing and cancer treatment in the era of precision medicine, but it also is a form of low-cost, high-value care,” the authors wrote.
The study was funded by a grant from the National Cancer Institute. Dr. Roberson disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA HEALTH FORUM
FDA approves trastuzumab-deruxtecan for HER2-low breast cancer
This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer, the FDA said in a press release.
The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it.
Approval was based on the DESTINY-Breast04 trial, which included 557 patients with unresectable or metastatic HER2-low breast cancer. The trial had two cohorts: 494 hormone receptor–positive (HR+) patients, and 63 hormone receptor–negative (HR–) patients.
Of these patients, 373 were randomly assigned to received trastuzumab deruxtecan every 3 weeks, and 184 were randomly assigned to receive physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel).
Among patients who received trastuzumab deruxtecan, progression-free survival was longer (10.1 months vs. 5.4 months), as was overall survival (23.9 months vs. 17.5 months), compared with those in the chemotherapy group.
“Overall, these results establish HER2-low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” Shanu Modi, MD, said in June at a press conference held during the annual meeting of the American Society of Clinical Oncology, where she presented the results.
The most common adverse reactions in the trial were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea. The agent carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.
The targeted agent is not recommended for women who are pregnant.
A version of this article first appeared on Medscape.com.
This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer, the FDA said in a press release.
The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it.
Approval was based on the DESTINY-Breast04 trial, which included 557 patients with unresectable or metastatic HER2-low breast cancer. The trial had two cohorts: 494 hormone receptor–positive (HR+) patients, and 63 hormone receptor–negative (HR–) patients.
Of these patients, 373 were randomly assigned to received trastuzumab deruxtecan every 3 weeks, and 184 were randomly assigned to receive physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel).
Among patients who received trastuzumab deruxtecan, progression-free survival was longer (10.1 months vs. 5.4 months), as was overall survival (23.9 months vs. 17.5 months), compared with those in the chemotherapy group.
“Overall, these results establish HER2-low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” Shanu Modi, MD, said in June at a press conference held during the annual meeting of the American Society of Clinical Oncology, where she presented the results.
The most common adverse reactions in the trial were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea. The agent carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.
The targeted agent is not recommended for women who are pregnant.
A version of this article first appeared on Medscape.com.
This is the first therapy approved for HER2-low breast cancer, a newly defined subset of HER2-negative breast cancer in which there are some HER2 proteins on the cell surface, but not enough to warrant classification as HER2-positive cancer, the FDA said in a press release.
The indication is for patients who have received prior chemotherapy in the metastatic setting or for patients whose cancer has returned during adjuvant chemotherapy or within 6 months of completing it.
Approval was based on the DESTINY-Breast04 trial, which included 557 patients with unresectable or metastatic HER2-low breast cancer. The trial had two cohorts: 494 hormone receptor–positive (HR+) patients, and 63 hormone receptor–negative (HR–) patients.
Of these patients, 373 were randomly assigned to received trastuzumab deruxtecan every 3 weeks, and 184 were randomly assigned to receive physician’s choice of chemotherapy (eribulin, capecitabine, gemcitabine, nab paclitaxel, or paclitaxel).
Among patients who received trastuzumab deruxtecan, progression-free survival was longer (10.1 months vs. 5.4 months), as was overall survival (23.9 months vs. 17.5 months), compared with those in the chemotherapy group.
“Overall, these results establish HER2-low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” Shanu Modi, MD, said in June at a press conference held during the annual meeting of the American Society of Clinical Oncology, where she presented the results.
The most common adverse reactions in the trial were nausea, fatigue, alopecia, vomiting, constipation, decreased appetite, musculoskeletal pain, and diarrhea. The agent carries a boxed warning regarding the risk of interstitial lung disease and embryo-fetal toxicity.
The targeted agent is not recommended for women who are pregnant.
A version of this article first appeared on Medscape.com.
Node-negative triple-negative breast cancer prognosis lies within stromal lymphocytes
and may be suitable candidates for reduced intensity pre- or postoperative chemotherapy, according to a team of European investigators.
Among 441 women in a Dutch cancer registry who were younger than 40 when they were diagnosed with node-negative TNBC and had not undergone systemic therapy, those who had 75% or more TILs in the intratumoral stromal area had a 15-year cumulative incidence of distant metastases or death of just 2.1%, and every 10% increase in sTILs was associated with a 19% decrease in the risk of death.
In contrast, the 15-year cumulative incidence of distant metastases was 38.4% for women with stromal TIL scores of less than 30%, according to researchers writing in the Journal of Clinical Oncology.
“These data could be used as a starting point for designing a randomized controlled chemotherapy de-escalation trial. The current study confirms the importance of sTILs as a valuable addition to the set of standard prognostic factors in patients with TNBC,” wrote the researchers, who were led by Sabine C. Linn, MD, of the Netherlands Cancer Institute, Amsterdam.
Markers for immune response
Stromal TILs, a mixture of mononuclear immune cells, have been shown in previous studies to be prognostic for outcomes in patients with early-stage TNBC treated either with or without neoadjuvant or adjuvant chemotherapy.
For example, investigators cited a study published in JCO in 2014, that showed among women with TNBC enrolled in the phase 3 ECOG 2197 clinical trial and the related ECOG 119 clinical trial, after a nearly 11-year follow-up, higher sTIL scores were associated with significantly better prognosis with every 10% increase translating into a 14% reduction in the risk of recurrence or death (P = .02).
“The prognostic importance of sTILs is, however, unexplored in patients diagnosed under age 40 years, let alone in the subgroup of systemic therapy–naive patients,” Dr. Linn and colleagues wrote.
Retrospective study
To see whether the prognostic value of sTILs was as strong among young, systemic therapy–naive women, the investigators conducted a retrospective study of women enrolled in the Netherlands Cancer Registry who were diagnosed with node-negative TNBC from 1989 to 2000. The patients selected had undergone only locoregional treatment, including axillary node dissection, but had not received any systemic therapy.
Pathologists reviewed samples, with TILs reported for the stromal compartment. The samples were grouped by sTIL score categories of high (75% or greater), intermediate (30% to less than 75%), or low (less than 30%). The investigators looked at overall survival (OS) and distant metastasis-free survival (DMFS) stratified by sTIL scores,
During a median follow-up of 15 years, 107 women died or developed distant metastases, and 78 experienced a second primary cancer.
The results were as noted, with patients in the highest category of sTILs having very low rates of either death or distant metastases during follow-up.
“We confirm the prognostic value of sTILs in young patients with early-stage N0 TNBC who are systemic therapy naive by taking advantage of a prospectively collected population-based cohort. Increasing sTILs are significantly associated with improved OS and DMFS. Patients with high sTILs (> 75%) had an excellent 10-year overall survival and a very low 10-year incidence of distant metastasis or death.
The study was supported by grants from The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, Agilent Technologies, the Dutch Cancer Society, and Breast Cancer Research Foundation. Dr. Linn reported consulting with and receiving compensation from Daiichi Sankyo, as well as receiving research funding from Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Tesaro, Merck, Immunomedics, Eurocept Pharmaceuticals, Agendia, and Novartis.
and may be suitable candidates for reduced intensity pre- or postoperative chemotherapy, according to a team of European investigators.
Among 441 women in a Dutch cancer registry who were younger than 40 when they were diagnosed with node-negative TNBC and had not undergone systemic therapy, those who had 75% or more TILs in the intratumoral stromal area had a 15-year cumulative incidence of distant metastases or death of just 2.1%, and every 10% increase in sTILs was associated with a 19% decrease in the risk of death.
In contrast, the 15-year cumulative incidence of distant metastases was 38.4% for women with stromal TIL scores of less than 30%, according to researchers writing in the Journal of Clinical Oncology.
“These data could be used as a starting point for designing a randomized controlled chemotherapy de-escalation trial. The current study confirms the importance of sTILs as a valuable addition to the set of standard prognostic factors in patients with TNBC,” wrote the researchers, who were led by Sabine C. Linn, MD, of the Netherlands Cancer Institute, Amsterdam.
Markers for immune response
Stromal TILs, a mixture of mononuclear immune cells, have been shown in previous studies to be prognostic for outcomes in patients with early-stage TNBC treated either with or without neoadjuvant or adjuvant chemotherapy.
For example, investigators cited a study published in JCO in 2014, that showed among women with TNBC enrolled in the phase 3 ECOG 2197 clinical trial and the related ECOG 119 clinical trial, after a nearly 11-year follow-up, higher sTIL scores were associated with significantly better prognosis with every 10% increase translating into a 14% reduction in the risk of recurrence or death (P = .02).
“The prognostic importance of sTILs is, however, unexplored in patients diagnosed under age 40 years, let alone in the subgroup of systemic therapy–naive patients,” Dr. Linn and colleagues wrote.
Retrospective study
To see whether the prognostic value of sTILs was as strong among young, systemic therapy–naive women, the investigators conducted a retrospective study of women enrolled in the Netherlands Cancer Registry who were diagnosed with node-negative TNBC from 1989 to 2000. The patients selected had undergone only locoregional treatment, including axillary node dissection, but had not received any systemic therapy.
Pathologists reviewed samples, with TILs reported for the stromal compartment. The samples were grouped by sTIL score categories of high (75% or greater), intermediate (30% to less than 75%), or low (less than 30%). The investigators looked at overall survival (OS) and distant metastasis-free survival (DMFS) stratified by sTIL scores,
During a median follow-up of 15 years, 107 women died or developed distant metastases, and 78 experienced a second primary cancer.
The results were as noted, with patients in the highest category of sTILs having very low rates of either death or distant metastases during follow-up.
“We confirm the prognostic value of sTILs in young patients with early-stage N0 TNBC who are systemic therapy naive by taking advantage of a prospectively collected population-based cohort. Increasing sTILs are significantly associated with improved OS and DMFS. Patients with high sTILs (> 75%) had an excellent 10-year overall survival and a very low 10-year incidence of distant metastasis or death.
The study was supported by grants from The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, Agilent Technologies, the Dutch Cancer Society, and Breast Cancer Research Foundation. Dr. Linn reported consulting with and receiving compensation from Daiichi Sankyo, as well as receiving research funding from Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Tesaro, Merck, Immunomedics, Eurocept Pharmaceuticals, Agendia, and Novartis.
and may be suitable candidates for reduced intensity pre- or postoperative chemotherapy, according to a team of European investigators.
Among 441 women in a Dutch cancer registry who were younger than 40 when they were diagnosed with node-negative TNBC and had not undergone systemic therapy, those who had 75% or more TILs in the intratumoral stromal area had a 15-year cumulative incidence of distant metastases or death of just 2.1%, and every 10% increase in sTILs was associated with a 19% decrease in the risk of death.
In contrast, the 15-year cumulative incidence of distant metastases was 38.4% for women with stromal TIL scores of less than 30%, according to researchers writing in the Journal of Clinical Oncology.
“These data could be used as a starting point for designing a randomized controlled chemotherapy de-escalation trial. The current study confirms the importance of sTILs as a valuable addition to the set of standard prognostic factors in patients with TNBC,” wrote the researchers, who were led by Sabine C. Linn, MD, of the Netherlands Cancer Institute, Amsterdam.
Markers for immune response
Stromal TILs, a mixture of mononuclear immune cells, have been shown in previous studies to be prognostic for outcomes in patients with early-stage TNBC treated either with or without neoadjuvant or adjuvant chemotherapy.
For example, investigators cited a study published in JCO in 2014, that showed among women with TNBC enrolled in the phase 3 ECOG 2197 clinical trial and the related ECOG 119 clinical trial, after a nearly 11-year follow-up, higher sTIL scores were associated with significantly better prognosis with every 10% increase translating into a 14% reduction in the risk of recurrence or death (P = .02).
“The prognostic importance of sTILs is, however, unexplored in patients diagnosed under age 40 years, let alone in the subgroup of systemic therapy–naive patients,” Dr. Linn and colleagues wrote.
Retrospective study
To see whether the prognostic value of sTILs was as strong among young, systemic therapy–naive women, the investigators conducted a retrospective study of women enrolled in the Netherlands Cancer Registry who were diagnosed with node-negative TNBC from 1989 to 2000. The patients selected had undergone only locoregional treatment, including axillary node dissection, but had not received any systemic therapy.
Pathologists reviewed samples, with TILs reported for the stromal compartment. The samples were grouped by sTIL score categories of high (75% or greater), intermediate (30% to less than 75%), or low (less than 30%). The investigators looked at overall survival (OS) and distant metastasis-free survival (DMFS) stratified by sTIL scores,
During a median follow-up of 15 years, 107 women died or developed distant metastases, and 78 experienced a second primary cancer.
The results were as noted, with patients in the highest category of sTILs having very low rates of either death or distant metastases during follow-up.
“We confirm the prognostic value of sTILs in young patients with early-stage N0 TNBC who are systemic therapy naive by taking advantage of a prospectively collected population-based cohort. Increasing sTILs are significantly associated with improved OS and DMFS. Patients with high sTILs (> 75%) had an excellent 10-year overall survival and a very low 10-year incidence of distant metastasis or death.
The study was supported by grants from The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, Agilent Technologies, the Dutch Cancer Society, and Breast Cancer Research Foundation. Dr. Linn reported consulting with and receiving compensation from Daiichi Sankyo, as well as receiving research funding from Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Tesaro, Merck, Immunomedics, Eurocept Pharmaceuticals, Agendia, and Novartis.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Commentary: Looking at Therapies for Patients With HER2-low Breast Cancer, August 2022
DESTINY-Breast04 is the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefit for patients with HER2-low metastatic breast cancer. This phase 3 study by Modi and colleagues enrolled 557 patients with hormone receptor (HR)–negative or HR-positive breast cancer and centrally confirmed HER2 low expression in those who had been previously treated with one or two prior lines of chemotherapy for metastatic breast cancer. Patients with HR-positive breast cancer were required to have endocrine therapy–refractory disease. Patients were randomized in a 2:1 ratio to receive either an antibody-drug conjugate, trastuzumab deruxtecan (T-DXd), or the physician's choice of standard chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nanoparticle albumin–bound paclitaxel [nab-paclitaxel]). Among all 557 patients, T-DXd improved median progression-free survival (PFS) by 4.8 months (9.9 vs 5.1 months; hazard ratio [HR] 0.50; P < .001) and median overall survival (OS) by 6.6 months (23.4 vs 16.8 months; HR 0.64; P = .0010) compared with standard single-agent chemotherapy. Among the 494 (88.7%) HR-positive patients, the median PFS was 10.1 months in the T-DXd group and 5.4 months in the chemotherapy group (HR 0.51; P < .001). Median OS was 23.9 months and 17.5 months, respectively (HR 0.64; P = .003). The rates of grade 3 or higher adverse events were lower with T-DXd than with standard chemotherapy (52.6% vs 67.4%, respectively), although higher rates of drug-related interstitial lung disease or pneumonitis were noted in the T-DXd arm (12.1% vs 0.1%). Lung toxicity continues to be an important safety concern with T-DXd. These practice-changing results open the door to a new treatment option for a substantial group of patients with HER2-low disease and support the need to reclassify HER2-low as a new targetable subset of breast cancer, distinct from HER-negative (HER2-0), and to acquire an understanding of the clinical characteristics of and prognosis for these patients.
Tarantino and colleagues evaluated the biologic and prognostic significance of HER2-low expression in breast cancer and investigated the association between HR status and HER2-low expression. Among 5235 patients with HER2-0 invasive breast cancer, HR expression was significantly more common among HER2-low tumors than among HER2-0 tumors (90.6% vs 81.8%; P < .001). The rate of HER2-low tumors increased progressively as estrogen receptor (ER) expression increased (40.1% of ER-negative, 46.3% of ER-low, 55.2% of ER-moderate, 57.8% of ER-high, and 62.1% of ER-very high [ie, ER > 95%] tumors; P < .001). Among 675 patients receiving neoadjuvant chemotherapy, higher pathologic complete response (pCR) rates were seen among those with HER2-0 tumors (26.8% vs 16.6%; P = .002), although no statistically significant differences in pCR rates were noted between HER2-low and HER2-0 tumors when analyzed by HR and ER status. In contrast to the findings of Modi and colleagues, this analysis saw no prognostic significance in terms of survival outcomes for HER2-low expression among patients who had HR-positive or HER2-0 tumors, suggesting that HER2-low breast cancer may not be a distinct biologic subtype. Further studies are needed to clarify whether HER2-low breast cancer needs to be considered separately in practice.
Immunotherapy, particular checkpoint inhibitors, has revolutionized the treatment of many solid tumors. However, their role in HER2-positive breast cancer remains unclear. IMpassion050 is a double-blind, randomized, phase 3 study evaluating the efficacy and safety of adding atezolizumab, an anti–programmed death-ligand 1 (PD-L1) antibody, to neoadjuvant standard of care (chemotherapy + pertuzumab + trastuzumab [PH]) for high-risk, HER2-positive early breast cancer (EBC). In the study by Huober and colleagues, 454 patients with a primary tumor > 2 cm and histologically confirmed positive lymph node status (N1-3) were randomly assigned in a 1:1 ratio to the atezolizumab or placebo group with dose-dense doxorubicin or cyclophosphamide, followed by paclitaxel and PH. In the adjuvant setting, patients continued atezolizumab or placebo and PH to complete 1 year of HER2-targeted therapy; those with residual disease could switch to trastuzumab emtansine with atezolizumab or placebo. At clinical cutoff (February 5, 2021), rates of pCR in the atezolizumab group vs placebo group were similar among all patients in the study (62.4% vs 62.7%; P = .9551) and in the PD-L1–positive population (64.2% vs 72.5%; P = .1846). Treatment-related grade 3-4 adverse events occurred more frequently in the atezolizumab group compared with the placebo group, both during the neoadjuvant treatment phase (47.3% vs 42.2%) and the adjuvant treatment phase (13.4% vs 9.8%).
In summary, the phase 3 IMpassion050 trial showed no significant improvement in pCR with the addition of atezolizumab to neoadjuvant therapy in patients with high-risk, HER2-positive EBC, including those with PD-L1–positive tumors. At this time, PH and chemotherapy remain the standard of care in this patient population. Longer follow-up is needed in respect to the long-term effect of atezolizumab in this setting.
DESTINY-Breast04 is the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefit for patients with HER2-low metastatic breast cancer. This phase 3 study by Modi and colleagues enrolled 557 patients with hormone receptor (HR)–negative or HR-positive breast cancer and centrally confirmed HER2 low expression in those who had been previously treated with one or two prior lines of chemotherapy for metastatic breast cancer. Patients with HR-positive breast cancer were required to have endocrine therapy–refractory disease. Patients were randomized in a 2:1 ratio to receive either an antibody-drug conjugate, trastuzumab deruxtecan (T-DXd), or the physician's choice of standard chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nanoparticle albumin–bound paclitaxel [nab-paclitaxel]). Among all 557 patients, T-DXd improved median progression-free survival (PFS) by 4.8 months (9.9 vs 5.1 months; hazard ratio [HR] 0.50; P < .001) and median overall survival (OS) by 6.6 months (23.4 vs 16.8 months; HR 0.64; P = .0010) compared with standard single-agent chemotherapy. Among the 494 (88.7%) HR-positive patients, the median PFS was 10.1 months in the T-DXd group and 5.4 months in the chemotherapy group (HR 0.51; P < .001). Median OS was 23.9 months and 17.5 months, respectively (HR 0.64; P = .003). The rates of grade 3 or higher adverse events were lower with T-DXd than with standard chemotherapy (52.6% vs 67.4%, respectively), although higher rates of drug-related interstitial lung disease or pneumonitis were noted in the T-DXd arm (12.1% vs 0.1%). Lung toxicity continues to be an important safety concern with T-DXd. These practice-changing results open the door to a new treatment option for a substantial group of patients with HER2-low disease and support the need to reclassify HER2-low as a new targetable subset of breast cancer, distinct from HER-negative (HER2-0), and to acquire an understanding of the clinical characteristics of and prognosis for these patients.
Tarantino and colleagues evaluated the biologic and prognostic significance of HER2-low expression in breast cancer and investigated the association between HR status and HER2-low expression. Among 5235 patients with HER2-0 invasive breast cancer, HR expression was significantly more common among HER2-low tumors than among HER2-0 tumors (90.6% vs 81.8%; P < .001). The rate of HER2-low tumors increased progressively as estrogen receptor (ER) expression increased (40.1% of ER-negative, 46.3% of ER-low, 55.2% of ER-moderate, 57.8% of ER-high, and 62.1% of ER-very high [ie, ER > 95%] tumors; P < .001). Among 675 patients receiving neoadjuvant chemotherapy, higher pathologic complete response (pCR) rates were seen among those with HER2-0 tumors (26.8% vs 16.6%; P = .002), although no statistically significant differences in pCR rates were noted between HER2-low and HER2-0 tumors when analyzed by HR and ER status. In contrast to the findings of Modi and colleagues, this analysis saw no prognostic significance in terms of survival outcomes for HER2-low expression among patients who had HR-positive or HER2-0 tumors, suggesting that HER2-low breast cancer may not be a distinct biologic subtype. Further studies are needed to clarify whether HER2-low breast cancer needs to be considered separately in practice.
Immunotherapy, particular checkpoint inhibitors, has revolutionized the treatment of many solid tumors. However, their role in HER2-positive breast cancer remains unclear. IMpassion050 is a double-blind, randomized, phase 3 study evaluating the efficacy and safety of adding atezolizumab, an anti–programmed death-ligand 1 (PD-L1) antibody, to neoadjuvant standard of care (chemotherapy + pertuzumab + trastuzumab [PH]) for high-risk, HER2-positive early breast cancer (EBC). In the study by Huober and colleagues, 454 patients with a primary tumor > 2 cm and histologically confirmed positive lymph node status (N1-3) were randomly assigned in a 1:1 ratio to the atezolizumab or placebo group with dose-dense doxorubicin or cyclophosphamide, followed by paclitaxel and PH. In the adjuvant setting, patients continued atezolizumab or placebo and PH to complete 1 year of HER2-targeted therapy; those with residual disease could switch to trastuzumab emtansine with atezolizumab or placebo. At clinical cutoff (February 5, 2021), rates of pCR in the atezolizumab group vs placebo group were similar among all patients in the study (62.4% vs 62.7%; P = .9551) and in the PD-L1–positive population (64.2% vs 72.5%; P = .1846). Treatment-related grade 3-4 adverse events occurred more frequently in the atezolizumab group compared with the placebo group, both during the neoadjuvant treatment phase (47.3% vs 42.2%) and the adjuvant treatment phase (13.4% vs 9.8%).
In summary, the phase 3 IMpassion050 trial showed no significant improvement in pCR with the addition of atezolizumab to neoadjuvant therapy in patients with high-risk, HER2-positive EBC, including those with PD-L1–positive tumors. At this time, PH and chemotherapy remain the standard of care in this patient population. Longer follow-up is needed in respect to the long-term effect of atezolizumab in this setting.
DESTINY-Breast04 is the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefit for patients with HER2-low metastatic breast cancer. This phase 3 study by Modi and colleagues enrolled 557 patients with hormone receptor (HR)–negative or HR-positive breast cancer and centrally confirmed HER2 low expression in those who had been previously treated with one or two prior lines of chemotherapy for metastatic breast cancer. Patients with HR-positive breast cancer were required to have endocrine therapy–refractory disease. Patients were randomized in a 2:1 ratio to receive either an antibody-drug conjugate, trastuzumab deruxtecan (T-DXd), or the physician's choice of standard chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nanoparticle albumin–bound paclitaxel [nab-paclitaxel]). Among all 557 patients, T-DXd improved median progression-free survival (PFS) by 4.8 months (9.9 vs 5.1 months; hazard ratio [HR] 0.50; P < .001) and median overall survival (OS) by 6.6 months (23.4 vs 16.8 months; HR 0.64; P = .0010) compared with standard single-agent chemotherapy. Among the 494 (88.7%) HR-positive patients, the median PFS was 10.1 months in the T-DXd group and 5.4 months in the chemotherapy group (HR 0.51; P < .001). Median OS was 23.9 months and 17.5 months, respectively (HR 0.64; P = .003). The rates of grade 3 or higher adverse events were lower with T-DXd than with standard chemotherapy (52.6% vs 67.4%, respectively), although higher rates of drug-related interstitial lung disease or pneumonitis were noted in the T-DXd arm (12.1% vs 0.1%). Lung toxicity continues to be an important safety concern with T-DXd. These practice-changing results open the door to a new treatment option for a substantial group of patients with HER2-low disease and support the need to reclassify HER2-low as a new targetable subset of breast cancer, distinct from HER-negative (HER2-0), and to acquire an understanding of the clinical characteristics of and prognosis for these patients.
Tarantino and colleagues evaluated the biologic and prognostic significance of HER2-low expression in breast cancer and investigated the association between HR status and HER2-low expression. Among 5235 patients with HER2-0 invasive breast cancer, HR expression was significantly more common among HER2-low tumors than among HER2-0 tumors (90.6% vs 81.8%; P < .001). The rate of HER2-low tumors increased progressively as estrogen receptor (ER) expression increased (40.1% of ER-negative, 46.3% of ER-low, 55.2% of ER-moderate, 57.8% of ER-high, and 62.1% of ER-very high [ie, ER > 95%] tumors; P < .001). Among 675 patients receiving neoadjuvant chemotherapy, higher pathologic complete response (pCR) rates were seen among those with HER2-0 tumors (26.8% vs 16.6%; P = .002), although no statistically significant differences in pCR rates were noted between HER2-low and HER2-0 tumors when analyzed by HR and ER status. In contrast to the findings of Modi and colleagues, this analysis saw no prognostic significance in terms of survival outcomes for HER2-low expression among patients who had HR-positive or HER2-0 tumors, suggesting that HER2-low breast cancer may not be a distinct biologic subtype. Further studies are needed to clarify whether HER2-low breast cancer needs to be considered separately in practice.
Immunotherapy, particular checkpoint inhibitors, has revolutionized the treatment of many solid tumors. However, their role in HER2-positive breast cancer remains unclear. IMpassion050 is a double-blind, randomized, phase 3 study evaluating the efficacy and safety of adding atezolizumab, an anti–programmed death-ligand 1 (PD-L1) antibody, to neoadjuvant standard of care (chemotherapy + pertuzumab + trastuzumab [PH]) for high-risk, HER2-positive early breast cancer (EBC). In the study by Huober and colleagues, 454 patients with a primary tumor > 2 cm and histologically confirmed positive lymph node status (N1-3) were randomly assigned in a 1:1 ratio to the atezolizumab or placebo group with dose-dense doxorubicin or cyclophosphamide, followed by paclitaxel and PH. In the adjuvant setting, patients continued atezolizumab or placebo and PH to complete 1 year of HER2-targeted therapy; those with residual disease could switch to trastuzumab emtansine with atezolizumab or placebo. At clinical cutoff (February 5, 2021), rates of pCR in the atezolizumab group vs placebo group were similar among all patients in the study (62.4% vs 62.7%; P = .9551) and in the PD-L1–positive population (64.2% vs 72.5%; P = .1846). Treatment-related grade 3-4 adverse events occurred more frequently in the atezolizumab group compared with the placebo group, both during the neoadjuvant treatment phase (47.3% vs 42.2%) and the adjuvant treatment phase (13.4% vs 9.8%).
In summary, the phase 3 IMpassion050 trial showed no significant improvement in pCR with the addition of atezolizumab to neoadjuvant therapy in patients with high-risk, HER2-positive EBC, including those with PD-L1–positive tumors. At this time, PH and chemotherapy remain the standard of care in this patient population. Longer follow-up is needed in respect to the long-term effect of atezolizumab in this setting.
Life and death decisions: What keeps oncologists up at night
It was 2 a.m. And Rebecca Shatsky, MD, could not sleep.
The breast oncologist was thinking about a patient of hers with metastatic cancer.
The patient’s disease had been asymptomatic for some time. Then without warning, her cancer suddenly exploded. Her bone marrow was failing, and her liver was not far behind.
Dr. Shatsky had a treatment plan ready to go but still, she felt uneasy.
“I had to be honest with her that I didn’t know if this plan would work,” says Dr. Shatsky, a medical oncologist at University of California, San Diego (UCSD).
That night, after visiting the patient in the hospital, Dr. Shatsky lay awake going over her next move, making sure it was the right one and hoping it would help keep the disease at bay.
“It’s so much pressure when someone is depending on you to make life or death decisions,” Dr. Shatsky said.
And in the quiet hours of night, these concerns grow louder.
Dr. Shatsky is not alone.
“There’s no off button,” says Aaron Goodman, MD, a hematologist at UCSD Health who goes by “Papa Heme” on Twitter. “I’m always thinking about my patients. Constantly.”
The public rarely gets a glimpse of these private moments. On occasion, oncologists will share a personal story, but more often, insights come from broad research on the ethical, emotional, and psychological toll of practicing medicine.
Many oncologists carry this baggage home with them because they have no other option.
“There is simply no time to process the weight of the day when I’ve got seven more patients who need my full attention before lunch,” Mark Lewis, MD, director, department of gastrointestinal oncology, Intermountain Healthcare, Salt Lake City, Utah. “That is why my processing happens outside of the office, when my brain can be quiet.”
What am I missing?
Dr. Goodman recognizes the gravity of each decision he makes. He pores over every detail of a patient’s scans, lab results, history, and symptoms.
But no matter how many times he checks and rechecks, one question nags at him: What am I missing?
For Dr. Goodman, this exhaustive level of attention is worth it.
“When errors are made, it’s someone’s life,” Dr. Goodman said. “Nothing would have prepared me for this responsibility. Until it lies on you, it’s impossible to understand how much trust patients put into us.”
That trust becomes most apparent for Dr. Goodman when facing a decision about how to treat a patient with acute myeloid leukemia who’s in remission.
Give more chemotherapy to root out the leukemia cells still lurking in the body, and the patient faces a high risk of the cancer returning. Pick stem cell transplant, and the chance of being cured goes up significantly, but the patient could also die within 100 days of the transplant.
“All together, the data show I’m helping patients with a transplant, but for the individual, I could be causing harm. Someone could be living less because of a decision I made,” Dr. Goodman said.
For patients with advanced cancer, oncologists may need to think several moves ahead. Mapping out a patient’s treatment options can feel like a game of chess. Dr. Shatsky is always trying to anticipate how the tumor will behave, what is driving it, and how lifestyle factors may influence a patient’s response in the present and the future.
“It is a mind game,” she says. “Like in chess, I try to outsmart my opponent. But with advanced cancer, there are not necessarily clear-cut guidelines or one way to manage the disease, and I have to do the best I can with drugs I have.”
That’s the art of oncology: Balancing the many knowns and unknowns of a person’s cancer alongside the toxicities of treatment and a patient’s hopes and goals.
Throughout the year, Don Dizon, MD, will see a number of patients with advanced disease. In these instances, the question he often wrestles with is if the patient can’t be cured, whether more treatment will just cause greater harm.
Dr. Dizon recently faced this dilemma with an older patient with metastatic disease who had not done well with an initial treatment regimen. After outlining the risks for more chemotherapy, he explained one option would be to forgo it and simply treat her symptoms.
“It’s an impossible choice,” says Dr. Dizon, director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, Providence.
Chemotherapy can provide symptom relief, but it can also be toxic – and patients may be so frail, they can die from more therapy.
“I told my patient, if in your heart, you want to try more therapy, that’s okay. But it’s also okay if you don’t,” Dr. Dizon recalled.
Her response: “You’re supposed to give me the answer.”
However, for patients approaching the end of life, there often is no right answer.
“It’s part of the discomfort you live with as a patient and oncologist, and when I leave the clinic, that’s one thing that follows me home,” Dr. Dizon said. “At the end of the day, I need to look in the mirror and know I did the best I could.”
The difficult conversation
Every Sunday, Dr. Lewis feels the weight of the week ahead. He and his wife, a pediatrician, call it the “Sunday scaries.”
It’s when Dr. Lewis begins thinking about the delicate conversations to come, rehearsing how he’s going to share the news that a person has advanced cancer or that a cancer, once in remission, has returned.
“Before the pandemic, I had 36 people come to a visit where I delivered some very heavy news and it became a Greek chorus of sobbing,” he recalls.
For every oncologist, delivering bad news is an integral part of the job. But after spending months, sometimes years, with a patient and the family, Dr. Lewis knows how to take the temperature of the room – who will likely prefer a more blunt style and who might need a gentler touch.
“The longer you know a patient and family, the better you can gauge the best approach,” Dr. Lewis said. “And for some, you know it’ll be complete devastation no matter what.”
When Jennifer Lycette, MD, prepares for a difficult conversation, she’ll run down all the possible ways it could go. Sometimes her brain will get stuck in a loop, cycling through the different trajectories on repeat.
“For years, I didn’t know how to cope with that,” said Dr. Lycette, medical director at Providence Oncology and Hematology Care Clinic in Seaside, Ore. “I wasn’t taught the tools to cope with that in my medical training. It took midcareer professional coaching that I sought out on my own to learn to remind myself that no matter what the person says, I have the experience and skill set to handle what comes next and to simply be present in the moment with the patient.”
The question that now sits with Dr. Lycette hours after a visit is what she could have done better. She knows from experience how important it is to choose her words carefully.
Early in her career, Dr. Lycette had a patient with stage IV cancer who wanted to know more about the death process. Because most people ask about pain, she assured him that he likely wouldn’t experience too much pain with his type of cancer.
“It will probably be like falling asleep,” said Dr. Lycette, hoping she was offering comfort. “When I saw him next, he told me he hadn’t slept.”
He was afraid that if he did, he wouldn’t wake up.
In that moment, Dr. Lycette realized the power that her words carry and the importance of trying to understand the inner lives of her patients.
Life outside the clinic
Sometimes an oncologist’s late-night ruminations have little to do with cancer itself.
Manali Patel, MD, finds herself worrying if her patients will have enough to eat and whether she will be able to help.
“I was up at 3 a.m. one morning, thinking about how we’re going to fund a project for patients from low-income households who we discovered were experiencing severe food insecurity – what grants we need, what foundations we can work with,” said Dr. Patel, a medical oncologist at Stanford Hospital and Clinics and the VA Palo Alto Health Care System in California.
The past few years of the pandemic have added a new layer of worry for Dr. Patel.
“I don’t want my patients to die from a preventable virus when they’ve already been through so much suffering,” Dr. Patel said.
This thought feeds worries about how her actions outside the clinic could unintentionally harm her patients. Should she go to a big medical conference? A family gathering? The grocery store?
“There are some places you can’t avoid, but these decisions have caused a lot of strife for me,” she said. “The health and safety of our patients – that’s in our wheelhouse – but so many of the policies are outside of our control.”
The inevitable losses and the wins
For patients with metastatic disease, eventually the treatment options will run out.
Dr. Shatsky likes to be up front with patients about that reality: “There will come a day when I will tell you there’s nothing more I can do, and you need to trust that I’m being honest with you and that’s the truth.”
For Dr. Goodman, the devastation that bad news brings patients and families is glaring. He knows there will be no more normalcy in their lives.
“I see a lot of suffering, but I know the suffering happens regardless of whether I see it or not,” Dr. Goodman said.
That’s why holding on to the victories can be so important. Dr. Goodman recalled a young patient who came to him with a 20-cm tumor and is now cured. “Had I not met that individual and done what I had done, he’d be dead, but now he’s going to live his life,” Dr. Goodman said. “But I don’t wake up at 2 a.m. thinking about that.”
Dr. Shatsky gets a lot of joy from the wins – the patients who do really well, the times when she can help a friend or colleagues – and those moments go a long way to outweigh the hurt, worry, and workload.
When dealing with so much gray, “the wins are important, knowing you can make a difference is important,” Dr. Dizon said.
And there’s a delicate balance.
“I think patients want an oncologist who cares and is genuinely invested in their outcomes but not someone who is so sad all the time,” Dr. Lewis said. “When I lose a patient, I still grieve each loss, but I can’t mourn every patient’s death like it’s a family member. Otherwise, I’d break.”
What would you do if you had terminal cancer?
Dr. Dizon recalled how a friend handled the news. She went home and made dinner, he said.
Ultimately, she lived for many years. She saw her kids get married, met her first grandchild, and had time to prepare, something not everyone gets the chance to do.
That’s why it’s important to “do what you normally do as long as you can,” Dr. Dizon said. “Live your life.”
A version of this article first appeared on Medscape.com.
It was 2 a.m. And Rebecca Shatsky, MD, could not sleep.
The breast oncologist was thinking about a patient of hers with metastatic cancer.
The patient’s disease had been asymptomatic for some time. Then without warning, her cancer suddenly exploded. Her bone marrow was failing, and her liver was not far behind.
Dr. Shatsky had a treatment plan ready to go but still, she felt uneasy.
“I had to be honest with her that I didn’t know if this plan would work,” says Dr. Shatsky, a medical oncologist at University of California, San Diego (UCSD).
That night, after visiting the patient in the hospital, Dr. Shatsky lay awake going over her next move, making sure it was the right one and hoping it would help keep the disease at bay.
“It’s so much pressure when someone is depending on you to make life or death decisions,” Dr. Shatsky said.
And in the quiet hours of night, these concerns grow louder.
Dr. Shatsky is not alone.
“There’s no off button,” says Aaron Goodman, MD, a hematologist at UCSD Health who goes by “Papa Heme” on Twitter. “I’m always thinking about my patients. Constantly.”
The public rarely gets a glimpse of these private moments. On occasion, oncologists will share a personal story, but more often, insights come from broad research on the ethical, emotional, and psychological toll of practicing medicine.
Many oncologists carry this baggage home with them because they have no other option.
“There is simply no time to process the weight of the day when I’ve got seven more patients who need my full attention before lunch,” Mark Lewis, MD, director, department of gastrointestinal oncology, Intermountain Healthcare, Salt Lake City, Utah. “That is why my processing happens outside of the office, when my brain can be quiet.”
What am I missing?
Dr. Goodman recognizes the gravity of each decision he makes. He pores over every detail of a patient’s scans, lab results, history, and symptoms.
But no matter how many times he checks and rechecks, one question nags at him: What am I missing?
For Dr. Goodman, this exhaustive level of attention is worth it.
“When errors are made, it’s someone’s life,” Dr. Goodman said. “Nothing would have prepared me for this responsibility. Until it lies on you, it’s impossible to understand how much trust patients put into us.”
That trust becomes most apparent for Dr. Goodman when facing a decision about how to treat a patient with acute myeloid leukemia who’s in remission.
Give more chemotherapy to root out the leukemia cells still lurking in the body, and the patient faces a high risk of the cancer returning. Pick stem cell transplant, and the chance of being cured goes up significantly, but the patient could also die within 100 days of the transplant.
“All together, the data show I’m helping patients with a transplant, but for the individual, I could be causing harm. Someone could be living less because of a decision I made,” Dr. Goodman said.
For patients with advanced cancer, oncologists may need to think several moves ahead. Mapping out a patient’s treatment options can feel like a game of chess. Dr. Shatsky is always trying to anticipate how the tumor will behave, what is driving it, and how lifestyle factors may influence a patient’s response in the present and the future.
“It is a mind game,” she says. “Like in chess, I try to outsmart my opponent. But with advanced cancer, there are not necessarily clear-cut guidelines or one way to manage the disease, and I have to do the best I can with drugs I have.”
That’s the art of oncology: Balancing the many knowns and unknowns of a person’s cancer alongside the toxicities of treatment and a patient’s hopes and goals.
Throughout the year, Don Dizon, MD, will see a number of patients with advanced disease. In these instances, the question he often wrestles with is if the patient can’t be cured, whether more treatment will just cause greater harm.
Dr. Dizon recently faced this dilemma with an older patient with metastatic disease who had not done well with an initial treatment regimen. After outlining the risks for more chemotherapy, he explained one option would be to forgo it and simply treat her symptoms.
“It’s an impossible choice,” says Dr. Dizon, director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, Providence.
Chemotherapy can provide symptom relief, but it can also be toxic – and patients may be so frail, they can die from more therapy.
“I told my patient, if in your heart, you want to try more therapy, that’s okay. But it’s also okay if you don’t,” Dr. Dizon recalled.
Her response: “You’re supposed to give me the answer.”
However, for patients approaching the end of life, there often is no right answer.
“It’s part of the discomfort you live with as a patient and oncologist, and when I leave the clinic, that’s one thing that follows me home,” Dr. Dizon said. “At the end of the day, I need to look in the mirror and know I did the best I could.”
The difficult conversation
Every Sunday, Dr. Lewis feels the weight of the week ahead. He and his wife, a pediatrician, call it the “Sunday scaries.”
It’s when Dr. Lewis begins thinking about the delicate conversations to come, rehearsing how he’s going to share the news that a person has advanced cancer or that a cancer, once in remission, has returned.
“Before the pandemic, I had 36 people come to a visit where I delivered some very heavy news and it became a Greek chorus of sobbing,” he recalls.
For every oncologist, delivering bad news is an integral part of the job. But after spending months, sometimes years, with a patient and the family, Dr. Lewis knows how to take the temperature of the room – who will likely prefer a more blunt style and who might need a gentler touch.
“The longer you know a patient and family, the better you can gauge the best approach,” Dr. Lewis said. “And for some, you know it’ll be complete devastation no matter what.”
When Jennifer Lycette, MD, prepares for a difficult conversation, she’ll run down all the possible ways it could go. Sometimes her brain will get stuck in a loop, cycling through the different trajectories on repeat.
“For years, I didn’t know how to cope with that,” said Dr. Lycette, medical director at Providence Oncology and Hematology Care Clinic in Seaside, Ore. “I wasn’t taught the tools to cope with that in my medical training. It took midcareer professional coaching that I sought out on my own to learn to remind myself that no matter what the person says, I have the experience and skill set to handle what comes next and to simply be present in the moment with the patient.”
The question that now sits with Dr. Lycette hours after a visit is what she could have done better. She knows from experience how important it is to choose her words carefully.
Early in her career, Dr. Lycette had a patient with stage IV cancer who wanted to know more about the death process. Because most people ask about pain, she assured him that he likely wouldn’t experience too much pain with his type of cancer.
“It will probably be like falling asleep,” said Dr. Lycette, hoping she was offering comfort. “When I saw him next, he told me he hadn’t slept.”
He was afraid that if he did, he wouldn’t wake up.
In that moment, Dr. Lycette realized the power that her words carry and the importance of trying to understand the inner lives of her patients.
Life outside the clinic
Sometimes an oncologist’s late-night ruminations have little to do with cancer itself.
Manali Patel, MD, finds herself worrying if her patients will have enough to eat and whether she will be able to help.
“I was up at 3 a.m. one morning, thinking about how we’re going to fund a project for patients from low-income households who we discovered were experiencing severe food insecurity – what grants we need, what foundations we can work with,” said Dr. Patel, a medical oncologist at Stanford Hospital and Clinics and the VA Palo Alto Health Care System in California.
The past few years of the pandemic have added a new layer of worry for Dr. Patel.
“I don’t want my patients to die from a preventable virus when they’ve already been through so much suffering,” Dr. Patel said.
This thought feeds worries about how her actions outside the clinic could unintentionally harm her patients. Should she go to a big medical conference? A family gathering? The grocery store?
“There are some places you can’t avoid, but these decisions have caused a lot of strife for me,” she said. “The health and safety of our patients – that’s in our wheelhouse – but so many of the policies are outside of our control.”
The inevitable losses and the wins
For patients with metastatic disease, eventually the treatment options will run out.
Dr. Shatsky likes to be up front with patients about that reality: “There will come a day when I will tell you there’s nothing more I can do, and you need to trust that I’m being honest with you and that’s the truth.”
For Dr. Goodman, the devastation that bad news brings patients and families is glaring. He knows there will be no more normalcy in their lives.
“I see a lot of suffering, but I know the suffering happens regardless of whether I see it or not,” Dr. Goodman said.
That’s why holding on to the victories can be so important. Dr. Goodman recalled a young patient who came to him with a 20-cm tumor and is now cured. “Had I not met that individual and done what I had done, he’d be dead, but now he’s going to live his life,” Dr. Goodman said. “But I don’t wake up at 2 a.m. thinking about that.”
Dr. Shatsky gets a lot of joy from the wins – the patients who do really well, the times when she can help a friend or colleagues – and those moments go a long way to outweigh the hurt, worry, and workload.
When dealing with so much gray, “the wins are important, knowing you can make a difference is important,” Dr. Dizon said.
And there’s a delicate balance.
“I think patients want an oncologist who cares and is genuinely invested in their outcomes but not someone who is so sad all the time,” Dr. Lewis said. “When I lose a patient, I still grieve each loss, but I can’t mourn every patient’s death like it’s a family member. Otherwise, I’d break.”
What would you do if you had terminal cancer?
Dr. Dizon recalled how a friend handled the news. She went home and made dinner, he said.
Ultimately, she lived for many years. She saw her kids get married, met her first grandchild, and had time to prepare, something not everyone gets the chance to do.
That’s why it’s important to “do what you normally do as long as you can,” Dr. Dizon said. “Live your life.”
A version of this article first appeared on Medscape.com.
It was 2 a.m. And Rebecca Shatsky, MD, could not sleep.
The breast oncologist was thinking about a patient of hers with metastatic cancer.
The patient’s disease had been asymptomatic for some time. Then without warning, her cancer suddenly exploded. Her bone marrow was failing, and her liver was not far behind.
Dr. Shatsky had a treatment plan ready to go but still, she felt uneasy.
“I had to be honest with her that I didn’t know if this plan would work,” says Dr. Shatsky, a medical oncologist at University of California, San Diego (UCSD).
That night, after visiting the patient in the hospital, Dr. Shatsky lay awake going over her next move, making sure it was the right one and hoping it would help keep the disease at bay.
“It’s so much pressure when someone is depending on you to make life or death decisions,” Dr. Shatsky said.
And in the quiet hours of night, these concerns grow louder.
Dr. Shatsky is not alone.
“There’s no off button,” says Aaron Goodman, MD, a hematologist at UCSD Health who goes by “Papa Heme” on Twitter. “I’m always thinking about my patients. Constantly.”
The public rarely gets a glimpse of these private moments. On occasion, oncologists will share a personal story, but more often, insights come from broad research on the ethical, emotional, and psychological toll of practicing medicine.
Many oncologists carry this baggage home with them because they have no other option.
“There is simply no time to process the weight of the day when I’ve got seven more patients who need my full attention before lunch,” Mark Lewis, MD, director, department of gastrointestinal oncology, Intermountain Healthcare, Salt Lake City, Utah. “That is why my processing happens outside of the office, when my brain can be quiet.”
What am I missing?
Dr. Goodman recognizes the gravity of each decision he makes. He pores over every detail of a patient’s scans, lab results, history, and symptoms.
But no matter how many times he checks and rechecks, one question nags at him: What am I missing?
For Dr. Goodman, this exhaustive level of attention is worth it.
“When errors are made, it’s someone’s life,” Dr. Goodman said. “Nothing would have prepared me for this responsibility. Until it lies on you, it’s impossible to understand how much trust patients put into us.”
That trust becomes most apparent for Dr. Goodman when facing a decision about how to treat a patient with acute myeloid leukemia who’s in remission.
Give more chemotherapy to root out the leukemia cells still lurking in the body, and the patient faces a high risk of the cancer returning. Pick stem cell transplant, and the chance of being cured goes up significantly, but the patient could also die within 100 days of the transplant.
“All together, the data show I’m helping patients with a transplant, but for the individual, I could be causing harm. Someone could be living less because of a decision I made,” Dr. Goodman said.
For patients with advanced cancer, oncologists may need to think several moves ahead. Mapping out a patient’s treatment options can feel like a game of chess. Dr. Shatsky is always trying to anticipate how the tumor will behave, what is driving it, and how lifestyle factors may influence a patient’s response in the present and the future.
“It is a mind game,” she says. “Like in chess, I try to outsmart my opponent. But with advanced cancer, there are not necessarily clear-cut guidelines or one way to manage the disease, and I have to do the best I can with drugs I have.”
That’s the art of oncology: Balancing the many knowns and unknowns of a person’s cancer alongside the toxicities of treatment and a patient’s hopes and goals.
Throughout the year, Don Dizon, MD, will see a number of patients with advanced disease. In these instances, the question he often wrestles with is if the patient can’t be cured, whether more treatment will just cause greater harm.
Dr. Dizon recently faced this dilemma with an older patient with metastatic disease who had not done well with an initial treatment regimen. After outlining the risks for more chemotherapy, he explained one option would be to forgo it and simply treat her symptoms.
“It’s an impossible choice,” says Dr. Dizon, director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, Providence.
Chemotherapy can provide symptom relief, but it can also be toxic – and patients may be so frail, they can die from more therapy.
“I told my patient, if in your heart, you want to try more therapy, that’s okay. But it’s also okay if you don’t,” Dr. Dizon recalled.
Her response: “You’re supposed to give me the answer.”
However, for patients approaching the end of life, there often is no right answer.
“It’s part of the discomfort you live with as a patient and oncologist, and when I leave the clinic, that’s one thing that follows me home,” Dr. Dizon said. “At the end of the day, I need to look in the mirror and know I did the best I could.”
The difficult conversation
Every Sunday, Dr. Lewis feels the weight of the week ahead. He and his wife, a pediatrician, call it the “Sunday scaries.”
It’s when Dr. Lewis begins thinking about the delicate conversations to come, rehearsing how he’s going to share the news that a person has advanced cancer or that a cancer, once in remission, has returned.
“Before the pandemic, I had 36 people come to a visit where I delivered some very heavy news and it became a Greek chorus of sobbing,” he recalls.
For every oncologist, delivering bad news is an integral part of the job. But after spending months, sometimes years, with a patient and the family, Dr. Lewis knows how to take the temperature of the room – who will likely prefer a more blunt style and who might need a gentler touch.
“The longer you know a patient and family, the better you can gauge the best approach,” Dr. Lewis said. “And for some, you know it’ll be complete devastation no matter what.”
When Jennifer Lycette, MD, prepares for a difficult conversation, she’ll run down all the possible ways it could go. Sometimes her brain will get stuck in a loop, cycling through the different trajectories on repeat.
“For years, I didn’t know how to cope with that,” said Dr. Lycette, medical director at Providence Oncology and Hematology Care Clinic in Seaside, Ore. “I wasn’t taught the tools to cope with that in my medical training. It took midcareer professional coaching that I sought out on my own to learn to remind myself that no matter what the person says, I have the experience and skill set to handle what comes next and to simply be present in the moment with the patient.”
The question that now sits with Dr. Lycette hours after a visit is what she could have done better. She knows from experience how important it is to choose her words carefully.
Early in her career, Dr. Lycette had a patient with stage IV cancer who wanted to know more about the death process. Because most people ask about pain, she assured him that he likely wouldn’t experience too much pain with his type of cancer.
“It will probably be like falling asleep,” said Dr. Lycette, hoping she was offering comfort. “When I saw him next, he told me he hadn’t slept.”
He was afraid that if he did, he wouldn’t wake up.
In that moment, Dr. Lycette realized the power that her words carry and the importance of trying to understand the inner lives of her patients.
Life outside the clinic
Sometimes an oncologist’s late-night ruminations have little to do with cancer itself.
Manali Patel, MD, finds herself worrying if her patients will have enough to eat and whether she will be able to help.
“I was up at 3 a.m. one morning, thinking about how we’re going to fund a project for patients from low-income households who we discovered were experiencing severe food insecurity – what grants we need, what foundations we can work with,” said Dr. Patel, a medical oncologist at Stanford Hospital and Clinics and the VA Palo Alto Health Care System in California.
The past few years of the pandemic have added a new layer of worry for Dr. Patel.
“I don’t want my patients to die from a preventable virus when they’ve already been through so much suffering,” Dr. Patel said.
This thought feeds worries about how her actions outside the clinic could unintentionally harm her patients. Should she go to a big medical conference? A family gathering? The grocery store?
“There are some places you can’t avoid, but these decisions have caused a lot of strife for me,” she said. “The health and safety of our patients – that’s in our wheelhouse – but so many of the policies are outside of our control.”
The inevitable losses and the wins
For patients with metastatic disease, eventually the treatment options will run out.
Dr. Shatsky likes to be up front with patients about that reality: “There will come a day when I will tell you there’s nothing more I can do, and you need to trust that I’m being honest with you and that’s the truth.”
For Dr. Goodman, the devastation that bad news brings patients and families is glaring. He knows there will be no more normalcy in their lives.
“I see a lot of suffering, but I know the suffering happens regardless of whether I see it or not,” Dr. Goodman said.
That’s why holding on to the victories can be so important. Dr. Goodman recalled a young patient who came to him with a 20-cm tumor and is now cured. “Had I not met that individual and done what I had done, he’d be dead, but now he’s going to live his life,” Dr. Goodman said. “But I don’t wake up at 2 a.m. thinking about that.”
Dr. Shatsky gets a lot of joy from the wins – the patients who do really well, the times when she can help a friend or colleagues – and those moments go a long way to outweigh the hurt, worry, and workload.
When dealing with so much gray, “the wins are important, knowing you can make a difference is important,” Dr. Dizon said.
And there’s a delicate balance.
“I think patients want an oncologist who cares and is genuinely invested in their outcomes but not someone who is so sad all the time,” Dr. Lewis said. “When I lose a patient, I still grieve each loss, but I can’t mourn every patient’s death like it’s a family member. Otherwise, I’d break.”
What would you do if you had terminal cancer?
Dr. Dizon recalled how a friend handled the news. She went home and made dinner, he said.
Ultimately, she lived for many years. She saw her kids get married, met her first grandchild, and had time to prepare, something not everyone gets the chance to do.
That’s why it’s important to “do what you normally do as long as you can,” Dr. Dizon said. “Live your life.”
A version of this article first appeared on Medscape.com.
ERBB2-low BC may not be a distinct biologic subtype
Key clinical point: Human epidermal growth factor receptor 2 (ERBB2)-low breast cancer (BC) cannot be considered a distinct biologic subtype of BC because most of its clinicopathologic and prognostic differences are associated with hormone receptor (HR) expression.
Major finding: HR expression was a significant factor associated with the ERBB2 status (adjusted odds ratio for HR-positive vs HR-negative tumors 2.1; P < .001). The pathologic complete response rate was similar in ERBB2-low and ERBB2-0 tumors among patients with HR-positive (P = .08) or triple-negative (P = .40) BC.
Study details: Findings are from a large cohort study including 5235 patients with ERBB2-negative invasive, stage I-III BC, of which 55.7% and 44.3% of patients had ERBB2-low and ERBB2-0 tumors, respectively.
Disclosures: Dr. Tarantino was supported by an American-Italian Cancer Foundation postdoctoral research fellowship. The authors declared serving on advisory boards of or receiving personal fees, research grants, consulting fees, or honoraria from several sources.
Source: Tarantino P et al. Prognostic and biologic significance of ERBB2-low expression in early-stage breast cancer. JAMA Oncol. 2022 (Jun 23). Doi: 10.1001/jamaoncol.2022.2286
Key clinical point: Human epidermal growth factor receptor 2 (ERBB2)-low breast cancer (BC) cannot be considered a distinct biologic subtype of BC because most of its clinicopathologic and prognostic differences are associated with hormone receptor (HR) expression.
Major finding: HR expression was a significant factor associated with the ERBB2 status (adjusted odds ratio for HR-positive vs HR-negative tumors 2.1; P < .001). The pathologic complete response rate was similar in ERBB2-low and ERBB2-0 tumors among patients with HR-positive (P = .08) or triple-negative (P = .40) BC.
Study details: Findings are from a large cohort study including 5235 patients with ERBB2-negative invasive, stage I-III BC, of which 55.7% and 44.3% of patients had ERBB2-low and ERBB2-0 tumors, respectively.
Disclosures: Dr. Tarantino was supported by an American-Italian Cancer Foundation postdoctoral research fellowship. The authors declared serving on advisory boards of or receiving personal fees, research grants, consulting fees, or honoraria from several sources.
Source: Tarantino P et al. Prognostic and biologic significance of ERBB2-low expression in early-stage breast cancer. JAMA Oncol. 2022 (Jun 23). Doi: 10.1001/jamaoncol.2022.2286
Key clinical point: Human epidermal growth factor receptor 2 (ERBB2)-low breast cancer (BC) cannot be considered a distinct biologic subtype of BC because most of its clinicopathologic and prognostic differences are associated with hormone receptor (HR) expression.
Major finding: HR expression was a significant factor associated with the ERBB2 status (adjusted odds ratio for HR-positive vs HR-negative tumors 2.1; P < .001). The pathologic complete response rate was similar in ERBB2-low and ERBB2-0 tumors among patients with HR-positive (P = .08) or triple-negative (P = .40) BC.
Study details: Findings are from a large cohort study including 5235 patients with ERBB2-negative invasive, stage I-III BC, of which 55.7% and 44.3% of patients had ERBB2-low and ERBB2-0 tumors, respectively.
Disclosures: Dr. Tarantino was supported by an American-Italian Cancer Foundation postdoctoral research fellowship. The authors declared serving on advisory boards of or receiving personal fees, research grants, consulting fees, or honoraria from several sources.
Source: Tarantino P et al. Prognostic and biologic significance of ERBB2-low expression in early-stage breast cancer. JAMA Oncol. 2022 (Jun 23). Doi: 10.1001/jamaoncol.2022.2286
β-blockers tied with decreased mortality in TNBC
Key clinical point: The use of β-blocker at the time of breast cancer (BC) diagnosis reduced mortality in patients with triple-negative BC (TNBC).
Major finding: Although β-blocker use vs no use was not associated with BC-specific survival in the overall population, β-blockers reduced BC mortality by 34% in patients with TNBC (hazard ratio [HR] 0.66; 95% CI 0.47-0.91). The meta-analysis further confirmed that β-blocker use was associated with progression/recurrence-free survival (HR 0.58; 95% CI 0.38-0.89) in the TNBC population.
Study details: Findings are from a large population-based cohort study including 30,060 women aged ≥ 50 years with primary invasive BC, of which 15% used β-blockers at the time of BC diagnosis, and from a meta-analysis of 8 observational studies.
Disclosures: This study was funded by the Norwegian Research Council and other sources. EK Sloan declared serving as a scientific advisory board member for Cygnal Therapeutics.
Source: Løfling LL et al. β-blockers and breast cancer survival by molecular subtypes: A population-based cohort study and meta-analysis. Br J Cancer. 2022 (Jun 20). Doi: 10.1038/s41416-022-01891-7
Key clinical point: The use of β-blocker at the time of breast cancer (BC) diagnosis reduced mortality in patients with triple-negative BC (TNBC).
Major finding: Although β-blocker use vs no use was not associated with BC-specific survival in the overall population, β-blockers reduced BC mortality by 34% in patients with TNBC (hazard ratio [HR] 0.66; 95% CI 0.47-0.91). The meta-analysis further confirmed that β-blocker use was associated with progression/recurrence-free survival (HR 0.58; 95% CI 0.38-0.89) in the TNBC population.
Study details: Findings are from a large population-based cohort study including 30,060 women aged ≥ 50 years with primary invasive BC, of which 15% used β-blockers at the time of BC diagnosis, and from a meta-analysis of 8 observational studies.
Disclosures: This study was funded by the Norwegian Research Council and other sources. EK Sloan declared serving as a scientific advisory board member for Cygnal Therapeutics.
Source: Løfling LL et al. β-blockers and breast cancer survival by molecular subtypes: A population-based cohort study and meta-analysis. Br J Cancer. 2022 (Jun 20). Doi: 10.1038/s41416-022-01891-7
Key clinical point: The use of β-blocker at the time of breast cancer (BC) diagnosis reduced mortality in patients with triple-negative BC (TNBC).
Major finding: Although β-blocker use vs no use was not associated with BC-specific survival in the overall population, β-blockers reduced BC mortality by 34% in patients with TNBC (hazard ratio [HR] 0.66; 95% CI 0.47-0.91). The meta-analysis further confirmed that β-blocker use was associated with progression/recurrence-free survival (HR 0.58; 95% CI 0.38-0.89) in the TNBC population.
Study details: Findings are from a large population-based cohort study including 30,060 women aged ≥ 50 years with primary invasive BC, of which 15% used β-blockers at the time of BC diagnosis, and from a meta-analysis of 8 observational studies.
Disclosures: This study was funded by the Norwegian Research Council and other sources. EK Sloan declared serving as a scientific advisory board member for Cygnal Therapeutics.
Source: Løfling LL et al. β-blockers and breast cancer survival by molecular subtypes: A population-based cohort study and meta-analysis. Br J Cancer. 2022 (Jun 20). Doi: 10.1038/s41416-022-01891-7
TNBC: Meta-analysis recommends lower dosage and higher frequency of capecitabine in the adjuvant setting
Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), capecitabine improved survival and demonstrated a tolerable safety profile, with lower dosage, higher frequency, and adjuvant setting being related with better survival outcomes.
Major finding: Capecitabine vs chemotherapy without capecitabine improved disease-free survival (DFS; hazard ratio [HR] 0.77; P < .001) and overall survival (HR 0.73; P < .0001). A lower dose (<1000 mg; HR 0.69; P = .002), a higher dosage frequency (≥6 cycles; HR 0.72; P < .0001) and an adjuvant setting (HR 0.74; P < .0001) were associated with a higher DFS. Capecitabine was associated with higher risk for diarrhea (P < .0001), hand-foot syndrome (P < .0001), and leukopenia (P < .01).
Study details: Findings are from a meta-analysis of 11 phase 3 randomized controlled trials including 5175 female patients with early-stage TNBC who received neoadjuvant or adjuvant chemotherapy with or without capecitabine.
Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.
Source: Xun X et al. Efficacy and safety of capecitabine for triple-negative breast cancer: A meta-analysis. Front Oncol. 2022;12:899423 (Jul 7). Doi: 10.3389/fonc.2022.899423
Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), capecitabine improved survival and demonstrated a tolerable safety profile, with lower dosage, higher frequency, and adjuvant setting being related with better survival outcomes.
Major finding: Capecitabine vs chemotherapy without capecitabine improved disease-free survival (DFS; hazard ratio [HR] 0.77; P < .001) and overall survival (HR 0.73; P < .0001). A lower dose (<1000 mg; HR 0.69; P = .002), a higher dosage frequency (≥6 cycles; HR 0.72; P < .0001) and an adjuvant setting (HR 0.74; P < .0001) were associated with a higher DFS. Capecitabine was associated with higher risk for diarrhea (P < .0001), hand-foot syndrome (P < .0001), and leukopenia (P < .01).
Study details: Findings are from a meta-analysis of 11 phase 3 randomized controlled trials including 5175 female patients with early-stage TNBC who received neoadjuvant or adjuvant chemotherapy with or without capecitabine.
Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.
Source: Xun X et al. Efficacy and safety of capecitabine for triple-negative breast cancer: A meta-analysis. Front Oncol. 2022;12:899423 (Jul 7). Doi: 10.3389/fonc.2022.899423
Key clinical point: In patients with early-stage triple-negative breast cancer (TNBC), capecitabine improved survival and demonstrated a tolerable safety profile, with lower dosage, higher frequency, and adjuvant setting being related with better survival outcomes.
Major finding: Capecitabine vs chemotherapy without capecitabine improved disease-free survival (DFS; hazard ratio [HR] 0.77; P < .001) and overall survival (HR 0.73; P < .0001). A lower dose (<1000 mg; HR 0.69; P = .002), a higher dosage frequency (≥6 cycles; HR 0.72; P < .0001) and an adjuvant setting (HR 0.74; P < .0001) were associated with a higher DFS. Capecitabine was associated with higher risk for diarrhea (P < .0001), hand-foot syndrome (P < .0001), and leukopenia (P < .01).
Study details: Findings are from a meta-analysis of 11 phase 3 randomized controlled trials including 5175 female patients with early-stage TNBC who received neoadjuvant or adjuvant chemotherapy with or without capecitabine.
Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.
Source: Xun X et al. Efficacy and safety of capecitabine for triple-negative breast cancer: A meta-analysis. Front Oncol. 2022;12:899423 (Jul 7). Doi: 10.3389/fonc.2022.899423