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FDA OKs selpercatinib for adults with RET-fusion+ solid tumors
that have progressed during or following systemic treatment, or for patients for whom there are no good alternative treatments.
In 2020, selpercatinib received accelerated approval for lung and thyroid RET-positive tumors; that approval transitioned to a regular approval for non–small cell lung cancer on Sept. 21. The latest approval expands the drug label to include an array of RET-positive tumor types, including pancreatic and colorectal cancers.
The approval was based on data from the phase 1/2 LIBRETTO-001 trial, which evaluated 41 patients with RET fusion–positive tumors. Thirty-seven patients (90%) had received prior systemic therapy, with almost one-third receiving three or more. Primary efficacy measures were overall response rate and duration of response.
Among the 41 patients, the overall response rate was 44%, with a duration of response of 24.5 months. Additionally, for 67% of patients, results lasted at least 6 months.
“In the LIBRETTO-001 trial, selpercatinib demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers,” Vivek Subbiah, MD, coinvestigator for the trial, said in a press release. “These data and FDA approval of the tumor-agnostic indication underscore the importance of routine, comprehensive genomic testing for patients across a wide variety of tumor types.”
The most common cancers in the study were pancreatic adenocarcinoma (27%), colorectal cancer (24%), and salivary cancer (10%).
The recommended selpercatinib dose, based on body weight, is 120 mg orally twice daily for people who weigh less than 110 pounds or 160 mg orally twice daily for who weigh 110 pounds or more.
The most common adverse reactions were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.
A version of this article first appeared on Medscape.com.
that have progressed during or following systemic treatment, or for patients for whom there are no good alternative treatments.
In 2020, selpercatinib received accelerated approval for lung and thyroid RET-positive tumors; that approval transitioned to a regular approval for non–small cell lung cancer on Sept. 21. The latest approval expands the drug label to include an array of RET-positive tumor types, including pancreatic and colorectal cancers.
The approval was based on data from the phase 1/2 LIBRETTO-001 trial, which evaluated 41 patients with RET fusion–positive tumors. Thirty-seven patients (90%) had received prior systemic therapy, with almost one-third receiving three or more. Primary efficacy measures were overall response rate and duration of response.
Among the 41 patients, the overall response rate was 44%, with a duration of response of 24.5 months. Additionally, for 67% of patients, results lasted at least 6 months.
“In the LIBRETTO-001 trial, selpercatinib demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers,” Vivek Subbiah, MD, coinvestigator for the trial, said in a press release. “These data and FDA approval of the tumor-agnostic indication underscore the importance of routine, comprehensive genomic testing for patients across a wide variety of tumor types.”
The most common cancers in the study were pancreatic adenocarcinoma (27%), colorectal cancer (24%), and salivary cancer (10%).
The recommended selpercatinib dose, based on body weight, is 120 mg orally twice daily for people who weigh less than 110 pounds or 160 mg orally twice daily for who weigh 110 pounds or more.
The most common adverse reactions were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.
A version of this article first appeared on Medscape.com.
that have progressed during or following systemic treatment, or for patients for whom there are no good alternative treatments.
In 2020, selpercatinib received accelerated approval for lung and thyroid RET-positive tumors; that approval transitioned to a regular approval for non–small cell lung cancer on Sept. 21. The latest approval expands the drug label to include an array of RET-positive tumor types, including pancreatic and colorectal cancers.
The approval was based on data from the phase 1/2 LIBRETTO-001 trial, which evaluated 41 patients with RET fusion–positive tumors. Thirty-seven patients (90%) had received prior systemic therapy, with almost one-third receiving three or more. Primary efficacy measures were overall response rate and duration of response.
Among the 41 patients, the overall response rate was 44%, with a duration of response of 24.5 months. Additionally, for 67% of patients, results lasted at least 6 months.
“In the LIBRETTO-001 trial, selpercatinib demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers,” Vivek Subbiah, MD, coinvestigator for the trial, said in a press release. “These data and FDA approval of the tumor-agnostic indication underscore the importance of routine, comprehensive genomic testing for patients across a wide variety of tumor types.”
The most common cancers in the study were pancreatic adenocarcinoma (27%), colorectal cancer (24%), and salivary cancer (10%).
The recommended selpercatinib dose, based on body weight, is 120 mg orally twice daily for people who weigh less than 110 pounds or 160 mg orally twice daily for who weigh 110 pounds or more.
The most common adverse reactions were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.
A version of this article first appeared on Medscape.com.
High BMI linked to better survival for cancer patients treated with ICI, but for men only
That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.
He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.
Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.
On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.
Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
The study data
The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m2; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.
For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).
Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.
That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.
He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.
Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.
On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.
Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
The study data
The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m2; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.
For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).
Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.
That is the conclusion of a new retrospective analysis presented during a poster session given at the annual meeting of the European Society for Medical Oncology. The study sought to better understand ICI outcomes. “These are complex new treatments and, because they harness the immune system, no two patients are likely to respond in the same way. BMI has previously been associated with improved survival in patients with advanced lung cancer treated with immunotherapy. However, the reasons behind this observation, and the implications for treatment are unknown, as is whether this observation is specific for patients with only certain types of cancers,” study author Dwight Owen, MD, said in an email.
He pointed out that the retrospective nature of the findings means that they have no immediate clinical implications. “The reason for the discrepancy in males remains unclear. Although our study included a relatively large number of patients, it is a heterogenous cohort and there may be confounding factors that we haven’t recognized, so these findings need to be replicated in larger cohorts,” said Dr. Owen, a medical oncologist with The Ohio State University Comprehensive Cancer Center, Columbus.
Asked if there is a potential biological explanation for a difference between males and females, Dr. Owen said that this is an area of intense research. One recent study examined whether androgen could help explain why men are more likely than women to both develop and have more aggressive nonreproductive cancers. They concluded that androgen receptor signaling may be leading to loss of effector and proliferative potential of CD8+ T cells in the tumor microenvironment. Once exhausted, these cells do not respond well to stimulation that can occur after ICI treatment.
On the opposite end of the spectrum, cancer cachexia is also a key subject of study. It is characterized by weight loss and is associated with worse clinical outcomes. A cachexia mouse model found that weight loss can lead to more clearance of immune checkpoint antibodies.
Still, much more work needs to be done. “For now, how BMI, obesity, and cachexia relate to other factors, for instance the microbiome and tumor immunogenicity, are still not fully understood,” Dr. Owen said.
The study data
The researchers analyzed data from 688 patients with metastatic cancer treated at their center between 2011 and 2017. 94% were White and 5% were Black. 41% were female and the mean age was 61.9 years. The mean BMI was 28.8 kg/m2; 40% of patients had melanoma, 23% had non–small cell lung cancer, 10% had renal cancer, and 27% had another form of cancer.
For every unit decrease in BMI, the researchers observed a 1.8% decrease in mortality (hazard ratio, 0.982; P = .007). Patients with a BMI of 40 or above had better survival than all other patients grouped by 5 BMI increments (that is, 35-40, 30-35, etc.). When separated by sex, males had a significant decrease in mortality for every increase in BMI unit (HR, 0.964; P = .004), but there was no significant difference among women (HR, 1.003; P = .706). The relationship in men held up after adjustment for Eastern Cooperative Oncology Group score, line of therapy, and cancer type (HR, 0.979; P = .0308). The researchers also looked at a separate cohort of 185 normal weight and 15 obese (BMI ≥ 40) NSCLC patients. Median survival was 27.5 months in the obese group and 9.1 months in the normal weight group (HR, 0.474; 95% CI, 0.232-0.969).
Dr. Owen has received research funding through his institution from Bristol-Myers Squibb, Genentech, Pfizer, Palobiofarma, and Onc.AI.
FROM ESMO CONGRESS 2022
A farewell to arms? Drug approvals based on single-arm trials can be flawed
PARIS – with results that should only be used, under certain conditions, for accelerated approvals that should then be followed by confirmatory studies.
In fact, many drugs approved over the last decade based solely on data from single-arm trials have been subsequently withdrawn when put through the rigors of a head-to-head randomized controlled trial, according to Bishal Gyawali, MD, PhD, from the department of oncology at Queen’s University, Kingston, Ont.
“Single-arm trials are not meant to provide confirmatory evidence sufficient for approval; However, that ship has sailed, and we have several drugs that are approved on the basis of single-arm trials, but we need to make sure that those approvals are accelerated or conditional approvals, not regular approval,” he said in a presentation included in a special session on drug approvals at the European Society for Medical Oncology Congress.
“We should not allow premature regular approval based on single-arm trials, because once a drug gets conditional approval, access is not an issue. Patients will have access to the drug anyway, but we should ensure that robust evidence follows, and long-term follow-up data are needed to develop confidence in the efficacy outcomes that are seen in single-arm trials,” he said.
In many cases, single-arm trials are large enough or of long enough duration that investigators could have reasonably performed a randomized controlled trial (RCT) in the first place, Dr. Gyawali added.
Why do single-arm trials?
The term “single-arm registration trial” is something of an oxymoron, he said, noting that the purpose of such trials should be whether to take the drug to a phase 3, randomized trial. But as authors of a 2019 study in JAMA Network Open showed, of a sample of phase 3 RCTs, 42% did not have a prior phase 2 trial, and 28% had a negative phase 2 trial. Single-arm trials may be acceptable for conditional drug approvals if all of the following conditions are met:
- A RCT is not possible because the disease is rare or randomization would be unethical.
- The safety of the drug is established and its potential benefits outweigh its risks.
- The drug is associated with a high and durable overall or objective response rate.
- The mechanism of action is supported by a strong scientific rationale, and if the drug may meet an unmet medical need.
Survival endpoints won’t do
Efficacy endpoints typically used in RCTs, such as progression-free survival (PFS) and overall survival (OS) can be misleading because they may be a result of the natural history of the disease and not the drug being tested, whereas ORRs are almost certainly reflective of the action of the drug itself, because spontaneous tumor regression is a rare phenomenon, Dr. Gyawali said.
He cautioned, however, that the ORR of placebo is not zero percent. For example in a 2018 study of sorafenib (Nexavar) versus placebo for advanced or refractory desmoid tumors, the ORR with the active drug was 33%, and the ORR for placebo was 20%.
It’s also open to question, he said, what constitutes an acceptably high ORR and duration of response, pointing to Food and Drug Administration accelerated approval of an indication for nivolumab (Opdivo) for treatment of patients with hepatocellular carcinoma (HCC) that had progressed on sorafenib. In the single-arm trial used as the basis for approval, the ORRs as assessed by an independent central review committee blinded to the results was 14.3%.
“So, nivolumab in hepatocellular cancer was approved on the basis of a response rate lower than that of placebo, albeit in a different tumor. But the point I’m trying to show here is we don’t have a good definition of what is a good response rate,” he said.
In July 2021, Bristol-Myers Squibb voluntarily withdrew the HCC indication for nivolumab, following negative results of the CheckMate 459 trial and a 5-4 vote against continuing the accelerated approval.
On second thought ...
Citing data compiled by Nathan I. Cherny, MD, from Shaare Zedek Medical Center, Jerusalem, Dr. Gyawali noted that 58 of 161 FDA approvals from 2017 to 2021 of drugs for adult solid tumors were based on single-arm trials. Of the 58 drugs, 39 received accelerated approvals, and 19 received regular approvals; of the 39 that received accelerated approvals, 4 were subsequently withdrawn, 8 were converted to regular approvals, and the remainder continued as accelerated approvals.
Interestingly, the median response rate among all the drugs was 40%, and did not differ between the type of approval received, suggesting that response rates are not predictive of whether a drug will receive a conditional or full-fledged go-ahead.
What’s rare and safe?
The definition of a rare disease in the United States is one that affects fewer than 40,000 per year, and in Europe it’s an incidence rate of less than 6 per 100,000 population, Dr. Gyawali noted. But he argued that even non–small cell lung cancer, the most common form of cancer in the world, could be considered rare if it is broken down into subtypes that are treated according to specific mutations that may occur in a relatively small number of patients.
He also noted that a specific drug’s safety, one of the most important criteria for granting approval to a drug based on a single-arm trial, can be difficult to judge without adequate controls for comparison.
Cherry-picking patients
Winette van der Graaf, MD, president of the European Organization for the Research and Treatment of Cancer, who attended the session where Dr. Gyawali’s presentation was played, said in an interview that clinicians should cast a critical eye on how trials are designed and conducted, including patient selection and choice of endpoints.
“One of the most obvious things to be concerned about is that we’re still having patients with good performance status enrolled, mostly PS 0 or 1, so how representative are these clinical trials for the patients we see in front of us on a daily basis?” she said.
“The other question is radiological endpoints, which we focus on with OS and PFS are most important for patients, especially if you consider that if patients may have asymptomatic disease, and we are only treating them with potentially toxic medication, what are we doing for them? Median overall survival when you look at all of these trials is only 4 months, so we really need to take into account how we affect patients in clinical trials,” she added.
Dr. van der Graaf emphasized that clinical trial investigators need to more routinely incorporate quality of life measures and other patient-reported outcomes in clinical trial results to help regulators and clinicians in practice get a better sense of the true clinical benefit of a new drug.
Dr. Gyawali did not disclose a funding source for his presentation. He reported consulting fees from Vivio Health and research grants from the American Society of Clinical Oncology. Dr. van der Graaf reported no conflicts of interest.
PARIS – with results that should only be used, under certain conditions, for accelerated approvals that should then be followed by confirmatory studies.
In fact, many drugs approved over the last decade based solely on data from single-arm trials have been subsequently withdrawn when put through the rigors of a head-to-head randomized controlled trial, according to Bishal Gyawali, MD, PhD, from the department of oncology at Queen’s University, Kingston, Ont.
“Single-arm trials are not meant to provide confirmatory evidence sufficient for approval; However, that ship has sailed, and we have several drugs that are approved on the basis of single-arm trials, but we need to make sure that those approvals are accelerated or conditional approvals, not regular approval,” he said in a presentation included in a special session on drug approvals at the European Society for Medical Oncology Congress.
“We should not allow premature regular approval based on single-arm trials, because once a drug gets conditional approval, access is not an issue. Patients will have access to the drug anyway, but we should ensure that robust evidence follows, and long-term follow-up data are needed to develop confidence in the efficacy outcomes that are seen in single-arm trials,” he said.
In many cases, single-arm trials are large enough or of long enough duration that investigators could have reasonably performed a randomized controlled trial (RCT) in the first place, Dr. Gyawali added.
Why do single-arm trials?
The term “single-arm registration trial” is something of an oxymoron, he said, noting that the purpose of such trials should be whether to take the drug to a phase 3, randomized trial. But as authors of a 2019 study in JAMA Network Open showed, of a sample of phase 3 RCTs, 42% did not have a prior phase 2 trial, and 28% had a negative phase 2 trial. Single-arm trials may be acceptable for conditional drug approvals if all of the following conditions are met:
- A RCT is not possible because the disease is rare or randomization would be unethical.
- The safety of the drug is established and its potential benefits outweigh its risks.
- The drug is associated with a high and durable overall or objective response rate.
- The mechanism of action is supported by a strong scientific rationale, and if the drug may meet an unmet medical need.
Survival endpoints won’t do
Efficacy endpoints typically used in RCTs, such as progression-free survival (PFS) and overall survival (OS) can be misleading because they may be a result of the natural history of the disease and not the drug being tested, whereas ORRs are almost certainly reflective of the action of the drug itself, because spontaneous tumor regression is a rare phenomenon, Dr. Gyawali said.
He cautioned, however, that the ORR of placebo is not zero percent. For example in a 2018 study of sorafenib (Nexavar) versus placebo for advanced or refractory desmoid tumors, the ORR with the active drug was 33%, and the ORR for placebo was 20%.
It’s also open to question, he said, what constitutes an acceptably high ORR and duration of response, pointing to Food and Drug Administration accelerated approval of an indication for nivolumab (Opdivo) for treatment of patients with hepatocellular carcinoma (HCC) that had progressed on sorafenib. In the single-arm trial used as the basis for approval, the ORRs as assessed by an independent central review committee blinded to the results was 14.3%.
“So, nivolumab in hepatocellular cancer was approved on the basis of a response rate lower than that of placebo, albeit in a different tumor. But the point I’m trying to show here is we don’t have a good definition of what is a good response rate,” he said.
In July 2021, Bristol-Myers Squibb voluntarily withdrew the HCC indication for nivolumab, following negative results of the CheckMate 459 trial and a 5-4 vote against continuing the accelerated approval.
On second thought ...
Citing data compiled by Nathan I. Cherny, MD, from Shaare Zedek Medical Center, Jerusalem, Dr. Gyawali noted that 58 of 161 FDA approvals from 2017 to 2021 of drugs for adult solid tumors were based on single-arm trials. Of the 58 drugs, 39 received accelerated approvals, and 19 received regular approvals; of the 39 that received accelerated approvals, 4 were subsequently withdrawn, 8 were converted to regular approvals, and the remainder continued as accelerated approvals.
Interestingly, the median response rate among all the drugs was 40%, and did not differ between the type of approval received, suggesting that response rates are not predictive of whether a drug will receive a conditional or full-fledged go-ahead.
What’s rare and safe?
The definition of a rare disease in the United States is one that affects fewer than 40,000 per year, and in Europe it’s an incidence rate of less than 6 per 100,000 population, Dr. Gyawali noted. But he argued that even non–small cell lung cancer, the most common form of cancer in the world, could be considered rare if it is broken down into subtypes that are treated according to specific mutations that may occur in a relatively small number of patients.
He also noted that a specific drug’s safety, one of the most important criteria for granting approval to a drug based on a single-arm trial, can be difficult to judge without adequate controls for comparison.
Cherry-picking patients
Winette van der Graaf, MD, president of the European Organization for the Research and Treatment of Cancer, who attended the session where Dr. Gyawali’s presentation was played, said in an interview that clinicians should cast a critical eye on how trials are designed and conducted, including patient selection and choice of endpoints.
“One of the most obvious things to be concerned about is that we’re still having patients with good performance status enrolled, mostly PS 0 or 1, so how representative are these clinical trials for the patients we see in front of us on a daily basis?” she said.
“The other question is radiological endpoints, which we focus on with OS and PFS are most important for patients, especially if you consider that if patients may have asymptomatic disease, and we are only treating them with potentially toxic medication, what are we doing for them? Median overall survival when you look at all of these trials is only 4 months, so we really need to take into account how we affect patients in clinical trials,” she added.
Dr. van der Graaf emphasized that clinical trial investigators need to more routinely incorporate quality of life measures and other patient-reported outcomes in clinical trial results to help regulators and clinicians in practice get a better sense of the true clinical benefit of a new drug.
Dr. Gyawali did not disclose a funding source for his presentation. He reported consulting fees from Vivio Health and research grants from the American Society of Clinical Oncology. Dr. van der Graaf reported no conflicts of interest.
PARIS – with results that should only be used, under certain conditions, for accelerated approvals that should then be followed by confirmatory studies.
In fact, many drugs approved over the last decade based solely on data from single-arm trials have been subsequently withdrawn when put through the rigors of a head-to-head randomized controlled trial, according to Bishal Gyawali, MD, PhD, from the department of oncology at Queen’s University, Kingston, Ont.
“Single-arm trials are not meant to provide confirmatory evidence sufficient for approval; However, that ship has sailed, and we have several drugs that are approved on the basis of single-arm trials, but we need to make sure that those approvals are accelerated or conditional approvals, not regular approval,” he said in a presentation included in a special session on drug approvals at the European Society for Medical Oncology Congress.
“We should not allow premature regular approval based on single-arm trials, because once a drug gets conditional approval, access is not an issue. Patients will have access to the drug anyway, but we should ensure that robust evidence follows, and long-term follow-up data are needed to develop confidence in the efficacy outcomes that are seen in single-arm trials,” he said.
In many cases, single-arm trials are large enough or of long enough duration that investigators could have reasonably performed a randomized controlled trial (RCT) in the first place, Dr. Gyawali added.
Why do single-arm trials?
The term “single-arm registration trial” is something of an oxymoron, he said, noting that the purpose of such trials should be whether to take the drug to a phase 3, randomized trial. But as authors of a 2019 study in JAMA Network Open showed, of a sample of phase 3 RCTs, 42% did not have a prior phase 2 trial, and 28% had a negative phase 2 trial. Single-arm trials may be acceptable for conditional drug approvals if all of the following conditions are met:
- A RCT is not possible because the disease is rare or randomization would be unethical.
- The safety of the drug is established and its potential benefits outweigh its risks.
- The drug is associated with a high and durable overall or objective response rate.
- The mechanism of action is supported by a strong scientific rationale, and if the drug may meet an unmet medical need.
Survival endpoints won’t do
Efficacy endpoints typically used in RCTs, such as progression-free survival (PFS) and overall survival (OS) can be misleading because they may be a result of the natural history of the disease and not the drug being tested, whereas ORRs are almost certainly reflective of the action of the drug itself, because spontaneous tumor regression is a rare phenomenon, Dr. Gyawali said.
He cautioned, however, that the ORR of placebo is not zero percent. For example in a 2018 study of sorafenib (Nexavar) versus placebo for advanced or refractory desmoid tumors, the ORR with the active drug was 33%, and the ORR for placebo was 20%.
It’s also open to question, he said, what constitutes an acceptably high ORR and duration of response, pointing to Food and Drug Administration accelerated approval of an indication for nivolumab (Opdivo) for treatment of patients with hepatocellular carcinoma (HCC) that had progressed on sorafenib. In the single-arm trial used as the basis for approval, the ORRs as assessed by an independent central review committee blinded to the results was 14.3%.
“So, nivolumab in hepatocellular cancer was approved on the basis of a response rate lower than that of placebo, albeit in a different tumor. But the point I’m trying to show here is we don’t have a good definition of what is a good response rate,” he said.
In July 2021, Bristol-Myers Squibb voluntarily withdrew the HCC indication for nivolumab, following negative results of the CheckMate 459 trial and a 5-4 vote against continuing the accelerated approval.
On second thought ...
Citing data compiled by Nathan I. Cherny, MD, from Shaare Zedek Medical Center, Jerusalem, Dr. Gyawali noted that 58 of 161 FDA approvals from 2017 to 2021 of drugs for adult solid tumors were based on single-arm trials. Of the 58 drugs, 39 received accelerated approvals, and 19 received regular approvals; of the 39 that received accelerated approvals, 4 were subsequently withdrawn, 8 were converted to regular approvals, and the remainder continued as accelerated approvals.
Interestingly, the median response rate among all the drugs was 40%, and did not differ between the type of approval received, suggesting that response rates are not predictive of whether a drug will receive a conditional or full-fledged go-ahead.
What’s rare and safe?
The definition of a rare disease in the United States is one that affects fewer than 40,000 per year, and in Europe it’s an incidence rate of less than 6 per 100,000 population, Dr. Gyawali noted. But he argued that even non–small cell lung cancer, the most common form of cancer in the world, could be considered rare if it is broken down into subtypes that are treated according to specific mutations that may occur in a relatively small number of patients.
He also noted that a specific drug’s safety, one of the most important criteria for granting approval to a drug based on a single-arm trial, can be difficult to judge without adequate controls for comparison.
Cherry-picking patients
Winette van der Graaf, MD, president of the European Organization for the Research and Treatment of Cancer, who attended the session where Dr. Gyawali’s presentation was played, said in an interview that clinicians should cast a critical eye on how trials are designed and conducted, including patient selection and choice of endpoints.
“One of the most obvious things to be concerned about is that we’re still having patients with good performance status enrolled, mostly PS 0 or 1, so how representative are these clinical trials for the patients we see in front of us on a daily basis?” she said.
“The other question is radiological endpoints, which we focus on with OS and PFS are most important for patients, especially if you consider that if patients may have asymptomatic disease, and we are only treating them with potentially toxic medication, what are we doing for them? Median overall survival when you look at all of these trials is only 4 months, so we really need to take into account how we affect patients in clinical trials,” she added.
Dr. van der Graaf emphasized that clinical trial investigators need to more routinely incorporate quality of life measures and other patient-reported outcomes in clinical trial results to help regulators and clinicians in practice get a better sense of the true clinical benefit of a new drug.
Dr. Gyawali did not disclose a funding source for his presentation. He reported consulting fees from Vivio Health and research grants from the American Society of Clinical Oncology. Dr. van der Graaf reported no conflicts of interest.
AT ESMO CONGRESS 2022
Time to cancer diagnoses in U.S. averages 5 months
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
Time to diagnosis is a crucial factor in cancer. Delays can lead to diagnosis at later stages and prevent optimal therapeutic strategies, both of which have the potential to reduce survival. An estimated 63%-82% of cancers get diagnosed as a result of symptom presentation, and delays in diagnosis can hamper treatment efforts. Diagnosis can be challenging because common symptoms – such as weight loss, weakness, poor appetite, and shortness of breath – are nonspecific.
A new analysis of U.S.-based data shows that the average time to diagnosis is 5.2 months for patients with solid tumors. The authors of the study call for better cancer diagnosis pathways in the U.S.
“Several countries, including the UK, Denmark, Sweden, Canada and Australia, have identified the importance and potential impact of more timely diagnosis by establishing national guidelines, special programs, and treatment pathways. However, in the U.S., there’s relatively little research and effort focused on streamlining the diagnostic pathway. Currently, the U.S. does not have established cancer diagnostic pathways that are used consistently,” Matthew Gitlin, PharmD, said during a presentation at the annual meeting of the European Society for Medical Oncology.
“That is often associated with worse clinical outcomes, increased economic burden, and decreased health related quality of life,” said Dr. Gitlin, founder and managing director of the health economics consulting firm BluePath Solutions, which conducted the analysis.
The study retrospectively examined administrative billing data drawn from the Clinformatics for Managed Markets longitudinal database. The data represent individuals in Medicare Advantage and a large, U.S.-based private insurance plan. Between 2018 and 2019, there were 458,818 cancer diagnoses. The mean age was 70.6 years and 49.6% of the patients were female. Sixty-five percent were White, 11.1% Black, 8.3% Hispanic, and 2.5% Asian. No race data were available for 13.2%. Medicare Advantage was the primary insurance carrier for 74.0%, and 24.0% had a commercial plan.
The mean time to diagnosis across all tumors was 5.2 months (standard deviation, 5.5 months). There was significant variation across different tumor types, as well as within the same tumor type. The median value was 3.9 months (interquartile range, 1.1-7.2 months).
Mean time to diagnosis ranged from 121.6 days for bladder cancer to as high as 229 days for multiple myeloma. Standard deviations were nearly as large or even larger than the mean values. The study showed that 15.8% of patients waited 6 months or longer for a diagnosis. Delays were most common in kidney cancer, colorectal cancer, gallbladder cancer, esophageal cancer, stomach cancer, lymphoma, and multiple myeloma: More than 25% of patients had a time to diagnosis of at least 6 months in these tumors.
“Although there is limited research in the published literature, our findings are consistent with that literature that does exist. Development or modification of policies, guidelines or medical interventions that streamline the diagnostic pathway are needed to optimize patient outcomes and reduce resource burden and cost to the health care system,” Dr. Gitlin said.
Previous literature on this topic has seen wide variation in how time to diagnosis is defined, and most research is conducted in high-income countries, according to Felipe Roitberg, PhD, who served as a discussant during the session. “Most of the countries and patients in need are localized in low- and middle-income countries, so that is a call to action (for more research),” said Dr. Roitberg, a clinical oncologist at Hospital Sírio Libanês in São Paulo, Brazil.
The study did not look at the associations between race and time to diagnosis. “This is a source of analysis could further be explored,” said Dr. Roitberg.
He noted that the ABC-DO prospective cohort study in sub-Saharan Africa found large variations in breast cancer survival by country, and its authors predicted that downstaging and improvements in treatment could prevent up to one-third of projected breast cancer deaths over the next decade. “So these are the drivers of populational gain in terms of overall survival – not more drugs, not more services available, but coordination of services and making sure the patient has a right pathway (to diagnosis and treatment),” Dr. Roitberg said.
Dr. Gitlin has received consulting fees from GRAIL LLC, which is a subsidiary of Illumina. Dr. Roitberg has received honoraria from Boehringer Ingelheim, Sanofi, Roche, MSD Oncology, AstraZeneca, Nestle Health Science, Dr Reddy’s, and Oncologia Brazil. He has consulted for MSD Oncology. He has received research funding from Roche, Boehringer Ingelheim, MSD, Bayer, AstraZeneca, and Takeda.
FROM ESMO CONGRESS 2022
Tumor-bed radiotherapy boost reduces DCIS recurrence risk
Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).
“ wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.
Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).
“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.
The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.
In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.
“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
Four-way trial
To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.
The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.
Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.
There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.
Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).
The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.
Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).
“ wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.
Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).
“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.
The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.
In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.
“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
Four-way trial
To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.
The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.
Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.
There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.
Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).
The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.
Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).
“ wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.
Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).
“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.
The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.
In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.
“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
Four-way trial
To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.
The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.
Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.
There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.
Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).
The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.
FROM THE LANCET
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.”
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
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.
Study confirms BRCA1 and BRCA2 linked to seven cancers
from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.
Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.
“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.
“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.
Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.
Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.
Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.
“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.
PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.
In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”
Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.
from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.
Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.
“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.
“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.
Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.
Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.
Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.
“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.
PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.
In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”
Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.
from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.
Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.
“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.
“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.
Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.
Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.
Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.
“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.
PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.
In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”
Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.
FROM JAMA ONCOLOGY