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‘Surprising’ lack of benefit to adding palbociclib to endocrine therapy in early HR+/HER2– breast cancer
Two years of adjuvant palbociclib added to endocrine therapy failed to improve invasive disease-free survival or any other efficacy endpoint in patients with stage II-III HR-positive, HER2-negative breast cancer.
“These definitive findings from the PALLAS trial, already indicated by an interim analysis, are surprising given the established efficacy of palbociclib and other CDK4/6i [inhibitors] in advanced breast cancer,” according to lead author Michael Gnant, MD, professor in the department of surgery, Medical University of Vienna, and colleagues.
The results from the PALLAS trial were presented Dec. 7 at the San Antonio Breast Cancer Symposium and simultaneously published in the Journal of Clinical Oncology.
At a median follow-up of 31 months and at the final protocol-defined analysis, invasive disease-free survival events occurred in 253 (8.8%) of 2,884 patients who received the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy and in 263 (9.1%) of 2,877 patients who received endocrine therapy alone. At 4 years, invasive disease-free survival rates were similar in the palbociclib group (84.2%) and standard treatment group (84.5%).
Caught by surprise
Studies have shown that combining CDK4/6 inhibitors and endocrine therapy prolongs progression-free survival (PFS) and overall survival in metastatic HR-positive, HER2-negative breast cancer, with good tolerability.
“CDK4/6 inhibitors have markedly changed outcomes in the metastatic setting and are now standard of care,” said Dr. Gnant, who presented the recent findings at SABCS. “It seem[ed] only logical to try to transfer these benefits to the curative setting of early breast cancer.”
But in 2020, palbociclib manufacturer Pfizer issued a press release noting that the PALLAS trial was unlikely to show a statistically significant improvement in the primary endpoint of invasive disease-free survival.
The results “caught many of us by surprise,” Kathy D. Miller, MD, codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis, wrote in response to this announcement.
The trial was based on strong science and incredibly positive results in the metastatic setting but did not meet its primary endpoint when incorporated into the adjuvant setting, Dr. Miller noted in a Medscape blog. “That is certainly not the result we had hoped for, and it’s not the result many of us were expecting.”
Dr. Miller emphasized that “more than anything else, this trial reminds us of the absolute necessity of putting our ideas to the test and doing appropriately powered, appropriately controlled, and well-conducted randomized trials.”
The PALLAS trial enrolled 5,796 patients from 406 centers in 21 countries worldwide over a 3-year period, with 5,761 included in the intention-to-treat population.
Participants were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone for at least 5 years.
Dr. Gnant and colleagues found that the primary endpoint – invasive disease-free survival – did not differ significantly different between the two treatment groups (hazard ratio, 0.96; P = .65). Secondary endpoints in the palbociclib versus no-palbociclib groups were also similar: 4-year survival rates for invasive breast cancer-free survival were 85.4% versus 86%, distant recurrence-free survival was 86.2% versus 87.8%, locoregional recurrence-free survival was 96.8% versus 95.4%, and overall survival was 93.8% versus 95.2%.
The main side effect of palbociclib was neutropenia, but there were no new safety signals, Dr. Gnant explained. He noted, however, that the rates of palbociclib discontinuation were monitored closely and were substantial. At 1 year, 30% of patients discontinued palbociclib and by 24 months, 45% had stopped.
Not the final word?
An interim analysis of the phase 3 monarchE trial did not align with the PALLAS trial.
The monarchE trial found that adding the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for 2 years significantly reduced the risk of early recurrence, compared with endocrine therapy alone in the same patient populations – those with early HR-positive, HER2-negative breast cancer. The researchers reported the combination was associated with a 25% relative risk reduction of invasive disease-free survival (HR, 0.75; P =.0096).
The research was presented at the ESMO Virtual Congress 2020 and simultaneously published in the Journal of Clinical Oncology.
Dr. Miller speculated how about how these two drugs that look so similar in the metastatic setting have given such different results in the adjuvant setting. One potential reason is pure chance.
“Any study, no matter how many zeros in the P value, could be simply the play of chance,” she said in an interview. “And that is true for negative and positive studies.”
The fault could also lie in the study design. “Remember, these are agents that we think of as reversing endocrine resistance and extending the benefit of hormone therapy,” she pointed out. “And yet we looked at very early results. Perhaps the study design was just wrong for palbociclib.”
Yet another possibility: The relative potency of those two CDK4/6 inhibitors could differ. “In a metastatic setting, that did not seem to affect effectiveness, but it clearly affected the toxicity profile. Perhaps in the adjuvant setting, those differences really do drive differences in efficacy,” she said.
Dr. Gnant also speculated that differences in the treatment schedules for the two drugs, as abemaciclib is taken continuously without a break, could potentially explain the different efficacies in the early breast cancer setting.
He called for long-term follow up, saying it’s essential for comprehensively examining outcomes in HR-positive luminal breast cancers.
“Ongoing analyses in the Trans-PALLAS translational and clinical science program, with almost 6,000 tumor blocks and tens of thousands of blood samples, will improve understanding of CD4/6 inhibition as well as contemporary management of HR-positive, HER2-negative breast cancer,” Dr. Gnant said.
The trial was funded by Pfizer, who provided study drug and financial support. In addition, the academic organizations ABCSG and AFT supported the trial by providing human resources. Dr. Gnant reported employment at Sandoz; receiving honoraria from Amgen, Novartis, AstraZeneca, Lilly; and consulting or advisory roles at Daiichi Sankyo, Veracyte, Tolmar¸ LifeBrain, and Lilly.
A version of this article first appeared on Medscape.com.
Two years of adjuvant palbociclib added to endocrine therapy failed to improve invasive disease-free survival or any other efficacy endpoint in patients with stage II-III HR-positive, HER2-negative breast cancer.
“These definitive findings from the PALLAS trial, already indicated by an interim analysis, are surprising given the established efficacy of palbociclib and other CDK4/6i [inhibitors] in advanced breast cancer,” according to lead author Michael Gnant, MD, professor in the department of surgery, Medical University of Vienna, and colleagues.
The results from the PALLAS trial were presented Dec. 7 at the San Antonio Breast Cancer Symposium and simultaneously published in the Journal of Clinical Oncology.
At a median follow-up of 31 months and at the final protocol-defined analysis, invasive disease-free survival events occurred in 253 (8.8%) of 2,884 patients who received the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy and in 263 (9.1%) of 2,877 patients who received endocrine therapy alone. At 4 years, invasive disease-free survival rates were similar in the palbociclib group (84.2%) and standard treatment group (84.5%).
Caught by surprise
Studies have shown that combining CDK4/6 inhibitors and endocrine therapy prolongs progression-free survival (PFS) and overall survival in metastatic HR-positive, HER2-negative breast cancer, with good tolerability.
“CDK4/6 inhibitors have markedly changed outcomes in the metastatic setting and are now standard of care,” said Dr. Gnant, who presented the recent findings at SABCS. “It seem[ed] only logical to try to transfer these benefits to the curative setting of early breast cancer.”
But in 2020, palbociclib manufacturer Pfizer issued a press release noting that the PALLAS trial was unlikely to show a statistically significant improvement in the primary endpoint of invasive disease-free survival.
The results “caught many of us by surprise,” Kathy D. Miller, MD, codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis, wrote in response to this announcement.
The trial was based on strong science and incredibly positive results in the metastatic setting but did not meet its primary endpoint when incorporated into the adjuvant setting, Dr. Miller noted in a Medscape blog. “That is certainly not the result we had hoped for, and it’s not the result many of us were expecting.”
Dr. Miller emphasized that “more than anything else, this trial reminds us of the absolute necessity of putting our ideas to the test and doing appropriately powered, appropriately controlled, and well-conducted randomized trials.”
The PALLAS trial enrolled 5,796 patients from 406 centers in 21 countries worldwide over a 3-year period, with 5,761 included in the intention-to-treat population.
Participants were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone for at least 5 years.
Dr. Gnant and colleagues found that the primary endpoint – invasive disease-free survival – did not differ significantly different between the two treatment groups (hazard ratio, 0.96; P = .65). Secondary endpoints in the palbociclib versus no-palbociclib groups were also similar: 4-year survival rates for invasive breast cancer-free survival were 85.4% versus 86%, distant recurrence-free survival was 86.2% versus 87.8%, locoregional recurrence-free survival was 96.8% versus 95.4%, and overall survival was 93.8% versus 95.2%.
The main side effect of palbociclib was neutropenia, but there were no new safety signals, Dr. Gnant explained. He noted, however, that the rates of palbociclib discontinuation were monitored closely and were substantial. At 1 year, 30% of patients discontinued palbociclib and by 24 months, 45% had stopped.
Not the final word?
An interim analysis of the phase 3 monarchE trial did not align with the PALLAS trial.
The monarchE trial found that adding the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for 2 years significantly reduced the risk of early recurrence, compared with endocrine therapy alone in the same patient populations – those with early HR-positive, HER2-negative breast cancer. The researchers reported the combination was associated with a 25% relative risk reduction of invasive disease-free survival (HR, 0.75; P =.0096).
The research was presented at the ESMO Virtual Congress 2020 and simultaneously published in the Journal of Clinical Oncology.
Dr. Miller speculated how about how these two drugs that look so similar in the metastatic setting have given such different results in the adjuvant setting. One potential reason is pure chance.
“Any study, no matter how many zeros in the P value, could be simply the play of chance,” she said in an interview. “And that is true for negative and positive studies.”
The fault could also lie in the study design. “Remember, these are agents that we think of as reversing endocrine resistance and extending the benefit of hormone therapy,” she pointed out. “And yet we looked at very early results. Perhaps the study design was just wrong for palbociclib.”
Yet another possibility: The relative potency of those two CDK4/6 inhibitors could differ. “In a metastatic setting, that did not seem to affect effectiveness, but it clearly affected the toxicity profile. Perhaps in the adjuvant setting, those differences really do drive differences in efficacy,” she said.
Dr. Gnant also speculated that differences in the treatment schedules for the two drugs, as abemaciclib is taken continuously without a break, could potentially explain the different efficacies in the early breast cancer setting.
He called for long-term follow up, saying it’s essential for comprehensively examining outcomes in HR-positive luminal breast cancers.
“Ongoing analyses in the Trans-PALLAS translational and clinical science program, with almost 6,000 tumor blocks and tens of thousands of blood samples, will improve understanding of CD4/6 inhibition as well as contemporary management of HR-positive, HER2-negative breast cancer,” Dr. Gnant said.
The trial was funded by Pfizer, who provided study drug and financial support. In addition, the academic organizations ABCSG and AFT supported the trial by providing human resources. Dr. Gnant reported employment at Sandoz; receiving honoraria from Amgen, Novartis, AstraZeneca, Lilly; and consulting or advisory roles at Daiichi Sankyo, Veracyte, Tolmar¸ LifeBrain, and Lilly.
A version of this article first appeared on Medscape.com.
Two years of adjuvant palbociclib added to endocrine therapy failed to improve invasive disease-free survival or any other efficacy endpoint in patients with stage II-III HR-positive, HER2-negative breast cancer.
“These definitive findings from the PALLAS trial, already indicated by an interim analysis, are surprising given the established efficacy of palbociclib and other CDK4/6i [inhibitors] in advanced breast cancer,” according to lead author Michael Gnant, MD, professor in the department of surgery, Medical University of Vienna, and colleagues.
The results from the PALLAS trial were presented Dec. 7 at the San Antonio Breast Cancer Symposium and simultaneously published in the Journal of Clinical Oncology.
At a median follow-up of 31 months and at the final protocol-defined analysis, invasive disease-free survival events occurred in 253 (8.8%) of 2,884 patients who received the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy and in 263 (9.1%) of 2,877 patients who received endocrine therapy alone. At 4 years, invasive disease-free survival rates were similar in the palbociclib group (84.2%) and standard treatment group (84.5%).
Caught by surprise
Studies have shown that combining CDK4/6 inhibitors and endocrine therapy prolongs progression-free survival (PFS) and overall survival in metastatic HR-positive, HER2-negative breast cancer, with good tolerability.
“CDK4/6 inhibitors have markedly changed outcomes in the metastatic setting and are now standard of care,” said Dr. Gnant, who presented the recent findings at SABCS. “It seem[ed] only logical to try to transfer these benefits to the curative setting of early breast cancer.”
But in 2020, palbociclib manufacturer Pfizer issued a press release noting that the PALLAS trial was unlikely to show a statistically significant improvement in the primary endpoint of invasive disease-free survival.
The results “caught many of us by surprise,” Kathy D. Miller, MD, codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis, wrote in response to this announcement.
The trial was based on strong science and incredibly positive results in the metastatic setting but did not meet its primary endpoint when incorporated into the adjuvant setting, Dr. Miller noted in a Medscape blog. “That is certainly not the result we had hoped for, and it’s not the result many of us were expecting.”
Dr. Miller emphasized that “more than anything else, this trial reminds us of the absolute necessity of putting our ideas to the test and doing appropriately powered, appropriately controlled, and well-conducted randomized trials.”
The PALLAS trial enrolled 5,796 patients from 406 centers in 21 countries worldwide over a 3-year period, with 5,761 included in the intention-to-treat population.
Participants were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone for at least 5 years.
Dr. Gnant and colleagues found that the primary endpoint – invasive disease-free survival – did not differ significantly different between the two treatment groups (hazard ratio, 0.96; P = .65). Secondary endpoints in the palbociclib versus no-palbociclib groups were also similar: 4-year survival rates for invasive breast cancer-free survival were 85.4% versus 86%, distant recurrence-free survival was 86.2% versus 87.8%, locoregional recurrence-free survival was 96.8% versus 95.4%, and overall survival was 93.8% versus 95.2%.
The main side effect of palbociclib was neutropenia, but there were no new safety signals, Dr. Gnant explained. He noted, however, that the rates of palbociclib discontinuation were monitored closely and were substantial. At 1 year, 30% of patients discontinued palbociclib and by 24 months, 45% had stopped.
Not the final word?
An interim analysis of the phase 3 monarchE trial did not align with the PALLAS trial.
The monarchE trial found that adding the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for 2 years significantly reduced the risk of early recurrence, compared with endocrine therapy alone in the same patient populations – those with early HR-positive, HER2-negative breast cancer. The researchers reported the combination was associated with a 25% relative risk reduction of invasive disease-free survival (HR, 0.75; P =.0096).
The research was presented at the ESMO Virtual Congress 2020 and simultaneously published in the Journal of Clinical Oncology.
Dr. Miller speculated how about how these two drugs that look so similar in the metastatic setting have given such different results in the adjuvant setting. One potential reason is pure chance.
“Any study, no matter how many zeros in the P value, could be simply the play of chance,” she said in an interview. “And that is true for negative and positive studies.”
The fault could also lie in the study design. “Remember, these are agents that we think of as reversing endocrine resistance and extending the benefit of hormone therapy,” she pointed out. “And yet we looked at very early results. Perhaps the study design was just wrong for palbociclib.”
Yet another possibility: The relative potency of those two CDK4/6 inhibitors could differ. “In a metastatic setting, that did not seem to affect effectiveness, but it clearly affected the toxicity profile. Perhaps in the adjuvant setting, those differences really do drive differences in efficacy,” she said.
Dr. Gnant also speculated that differences in the treatment schedules for the two drugs, as abemaciclib is taken continuously without a break, could potentially explain the different efficacies in the early breast cancer setting.
He called for long-term follow up, saying it’s essential for comprehensively examining outcomes in HR-positive luminal breast cancers.
“Ongoing analyses in the Trans-PALLAS translational and clinical science program, with almost 6,000 tumor blocks and tens of thousands of blood samples, will improve understanding of CD4/6 inhibition as well as contemporary management of HR-positive, HER2-negative breast cancer,” Dr. Gnant said.
The trial was funded by Pfizer, who provided study drug and financial support. In addition, the academic organizations ABCSG and AFT supported the trial by providing human resources. Dr. Gnant reported employment at Sandoz; receiving honoraria from Amgen, Novartis, AstraZeneca, Lilly; and consulting or advisory roles at Daiichi Sankyo, Veracyte, Tolmar¸ LifeBrain, and Lilly.
A version of this article first appeared on Medscape.com.
FROM SABCS 2021
Talk early to patients with high-risk AML about end-of-life decisions
The prognosis isn’t good for high-risk AML, defined in the study as either relapsing/recurrent disease or a diagnosis made past the age of 59 years. Almost 60% of the patients (114) died during the 7 years of the study, which started in 2014.
Therefore, it’s important to bring up end-of-life decisions when patients are still able to discuss them, so families aren’t left struggling to guess how aggressive their loved ones might have wanted their final care to be, said lead investigator Hannah Abrams, MD, an internal medicine resident at Massachusetts General. She presented these findings at the annual meeting of the American Society of Hematology.
Much of the time, however, end-of-life discussions come too late. The study team found that nearly 40% (45/114) of the patients who died during the study were not involved in their final code decisions, which most often were to administer comfort care only. Many patients were too ill to participate; the median time between the last code change and death was just 2 days.
Dr. Abrams said she’s seen how families agonize when patients haven’t addressed the issue beforehand. “Witnessing that made me think this is really important to look at. Having these conversations upfront is really important,” she said in an interview.
When asked for comment, hematologist-oncologist Toby Campbell, MD, chief of palliative care at the University of Wisconsin, Madison, agreed.
He called this issue a “missed opportunity for patient autonomy and self-determination. Patients with high-risk AML commonly experience rapid changes in their clinical condition, which catch everyone by surprise. Healthcare providers should do more to prepare patients and families, rather than allow them to be surprised,” Dr. Campbell said.
Part of the problem, Dr. Abrams said, is that end-of-life discussions can fall through the cracks amid urgent discussions about chemotherapy options and other matters.
“One of the biggest things to make this more feasible is to schedule and reimburse time in clinic for this to happen,” she said, noting a need to carve out and protect “15 minutes for patients and clinicians to talk about this.”
Another aspect is that patients are often overly optimistic about their prognoses, so end-of-life discussions don’t seem as pressing. Educational materials about the meaning of various code options and when they are appropriate could help, Dr. Abrams said.
As for the psychological impact of bringing up end-of-life decisions early on, Mikkael Sekeres, MD, chief of the division of hematology at the University of Miami, stressed the importance of telling patients, “We are having this conversation because you are doing well, not because you are doing poorly, and this is the time to have it.”
“Sometimes it does take a sentinel event like an ICU stay before some people want to engage in that conversation, and unfortunately, that is often too late,” said Dr. Sekeres, who moderated Dr. Abrams’ presentation at the meeting.
Among other findings, Dr. Abrams and her team reported that at diagnosis, 86.0% of patients were full-code, and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions during their illness.
Among patients who died, older age and receipt of non-intensive chemotherapy were associated with earlier discussions about code status.
The next step in the project is to determine if palliative care consults yield earlier discussions and greater patient involvement.
There was no commercial funding for the study, and Dr. Abrams and Dr. Campbell didn’t have any relevant disclosures. Dr. Sekeres is an advisor to Novartis, Takeda, and BMS.
aotto@mdedge.com
The prognosis isn’t good for high-risk AML, defined in the study as either relapsing/recurrent disease or a diagnosis made past the age of 59 years. Almost 60% of the patients (114) died during the 7 years of the study, which started in 2014.
Therefore, it’s important to bring up end-of-life decisions when patients are still able to discuss them, so families aren’t left struggling to guess how aggressive their loved ones might have wanted their final care to be, said lead investigator Hannah Abrams, MD, an internal medicine resident at Massachusetts General. She presented these findings at the annual meeting of the American Society of Hematology.
Much of the time, however, end-of-life discussions come too late. The study team found that nearly 40% (45/114) of the patients who died during the study were not involved in their final code decisions, which most often were to administer comfort care only. Many patients were too ill to participate; the median time between the last code change and death was just 2 days.
Dr. Abrams said she’s seen how families agonize when patients haven’t addressed the issue beforehand. “Witnessing that made me think this is really important to look at. Having these conversations upfront is really important,” she said in an interview.
When asked for comment, hematologist-oncologist Toby Campbell, MD, chief of palliative care at the University of Wisconsin, Madison, agreed.
He called this issue a “missed opportunity for patient autonomy and self-determination. Patients with high-risk AML commonly experience rapid changes in their clinical condition, which catch everyone by surprise. Healthcare providers should do more to prepare patients and families, rather than allow them to be surprised,” Dr. Campbell said.
Part of the problem, Dr. Abrams said, is that end-of-life discussions can fall through the cracks amid urgent discussions about chemotherapy options and other matters.
“One of the biggest things to make this more feasible is to schedule and reimburse time in clinic for this to happen,” she said, noting a need to carve out and protect “15 minutes for patients and clinicians to talk about this.”
Another aspect is that patients are often overly optimistic about their prognoses, so end-of-life discussions don’t seem as pressing. Educational materials about the meaning of various code options and when they are appropriate could help, Dr. Abrams said.
As for the psychological impact of bringing up end-of-life decisions early on, Mikkael Sekeres, MD, chief of the division of hematology at the University of Miami, stressed the importance of telling patients, “We are having this conversation because you are doing well, not because you are doing poorly, and this is the time to have it.”
“Sometimes it does take a sentinel event like an ICU stay before some people want to engage in that conversation, and unfortunately, that is often too late,” said Dr. Sekeres, who moderated Dr. Abrams’ presentation at the meeting.
Among other findings, Dr. Abrams and her team reported that at diagnosis, 86.0% of patients were full-code, and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions during their illness.
Among patients who died, older age and receipt of non-intensive chemotherapy were associated with earlier discussions about code status.
The next step in the project is to determine if palliative care consults yield earlier discussions and greater patient involvement.
There was no commercial funding for the study, and Dr. Abrams and Dr. Campbell didn’t have any relevant disclosures. Dr. Sekeres is an advisor to Novartis, Takeda, and BMS.
aotto@mdedge.com
The prognosis isn’t good for high-risk AML, defined in the study as either relapsing/recurrent disease or a diagnosis made past the age of 59 years. Almost 60% of the patients (114) died during the 7 years of the study, which started in 2014.
Therefore, it’s important to bring up end-of-life decisions when patients are still able to discuss them, so families aren’t left struggling to guess how aggressive their loved ones might have wanted their final care to be, said lead investigator Hannah Abrams, MD, an internal medicine resident at Massachusetts General. She presented these findings at the annual meeting of the American Society of Hematology.
Much of the time, however, end-of-life discussions come too late. The study team found that nearly 40% (45/114) of the patients who died during the study were not involved in their final code decisions, which most often were to administer comfort care only. Many patients were too ill to participate; the median time between the last code change and death was just 2 days.
Dr. Abrams said she’s seen how families agonize when patients haven’t addressed the issue beforehand. “Witnessing that made me think this is really important to look at. Having these conversations upfront is really important,” she said in an interview.
When asked for comment, hematologist-oncologist Toby Campbell, MD, chief of palliative care at the University of Wisconsin, Madison, agreed.
He called this issue a “missed opportunity for patient autonomy and self-determination. Patients with high-risk AML commonly experience rapid changes in their clinical condition, which catch everyone by surprise. Healthcare providers should do more to prepare patients and families, rather than allow them to be surprised,” Dr. Campbell said.
Part of the problem, Dr. Abrams said, is that end-of-life discussions can fall through the cracks amid urgent discussions about chemotherapy options and other matters.
“One of the biggest things to make this more feasible is to schedule and reimburse time in clinic for this to happen,” she said, noting a need to carve out and protect “15 minutes for patients and clinicians to talk about this.”
Another aspect is that patients are often overly optimistic about their prognoses, so end-of-life discussions don’t seem as pressing. Educational materials about the meaning of various code options and when they are appropriate could help, Dr. Abrams said.
As for the psychological impact of bringing up end-of-life decisions early on, Mikkael Sekeres, MD, chief of the division of hematology at the University of Miami, stressed the importance of telling patients, “We are having this conversation because you are doing well, not because you are doing poorly, and this is the time to have it.”
“Sometimes it does take a sentinel event like an ICU stay before some people want to engage in that conversation, and unfortunately, that is often too late,” said Dr. Sekeres, who moderated Dr. Abrams’ presentation at the meeting.
Among other findings, Dr. Abrams and her team reported that at diagnosis, 86.0% of patients were full-code, and 8.5% had restrictions on life-sustaining therapies. Overall, 57% (114/200) of patients experienced a code status transition, with a median of two transitions during their illness.
Among patients who died, older age and receipt of non-intensive chemotherapy were associated with earlier discussions about code status.
The next step in the project is to determine if palliative care consults yield earlier discussions and greater patient involvement.
There was no commercial funding for the study, and Dr. Abrams and Dr. Campbell didn’t have any relevant disclosures. Dr. Sekeres is an advisor to Novartis, Takeda, and BMS.
aotto@mdedge.com
FROM ASH 2021
Myeloid patients respond robustly to Moderna COVID vaccine
Factors including age, gender, race, disease status, lower-intensity active treatment, baseline neutrophil and lymphocyte counts, and past history of stem cell transplant had no effects on seroconversion in the study, which, despite its small numbers, is one of the largest series to date among patients with myeloid cancers. The findings were reported at the annual meeting of the American Society of Hematology.
COVID vaccination “appears to induce a strong antibody response” in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), unlike with B-cell malignancies. “It indicates we should be aggressive about vaccinating such patients,” said senior investigator Jeffrey Lancet, MD, a blood cancer specialist at Moffitt, when he presented the findings at the meeting.
Presentation moderator Laura Michaelis, MD, a hematologist-oncologist at the Medical College of Wisconsin, Milwaukee, agreed.
The “strong antibody response in this group,” coupled with its high risk for severe COVID, “confirm the importance of these patients getting vaccinated,” she said.
Thirty patients with AML and 16 with MDS were included in the review. Most patients were in remission at the time of vaccination, but a third were in active treatment, including six on hypomethylating agents, six on targeted therapies, two on luspatercept, and one on lenalidomide. Thirty-two patients (69.6%) were a median of 17 months past allogeneic stem cell transplant.
Overall, 69.6% of patients developed IgG against spike proteins after the first shot and 95.7% of patients after the second dose, with a large increase in titer levels from the first to the second dose, from a mean of 315 AU/mL to 3,806.5 AU/mL following the second dose.
“Lab and clinical variables did not affect the antibody positivity rate after the second dose,” but patients on steroids and other immunosuppressants seemed less likely to respond to the first shot, Dr. Lancet said.
The study, conducted in early 2021, did not include acutely ill patients or those undergoing cheomotherapy induction and other aggressive treatments, because such patients were not being vaccinated at Moffitt during the study period.
The investigators measured anti-spike IgG by ELISA at baseline, then again about a month after the first shot and a month after the second shot.
Side effects were common and typically mild, including injection site pain, fatigue, headache, and arm swelling. Two patients with AML relapsed after vaccination.
Patients were a median of 68 years old when they were vaccinated; 58.7% were men; and almost all of the subjects were White. The median time from diagnosis to the first shot was 2 years.
The next step in the project is to study the timing of vaccination and response to it among patients on aggressive treatment and to perform neutralizing antibody assays to correlate IgG response with protection from COVID.
No funding was reported for the study. Investigators had numerous industry ties, including Dr. Lancet, a consultant for Celgene/BMS, Millenium Pharma/Takeda, AbbVie, and other firms. Dr. Michaelis didn’t have any disclosures.
aotto@mdedge.com
Factors including age, gender, race, disease status, lower-intensity active treatment, baseline neutrophil and lymphocyte counts, and past history of stem cell transplant had no effects on seroconversion in the study, which, despite its small numbers, is one of the largest series to date among patients with myeloid cancers. The findings were reported at the annual meeting of the American Society of Hematology.
COVID vaccination “appears to induce a strong antibody response” in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), unlike with B-cell malignancies. “It indicates we should be aggressive about vaccinating such patients,” said senior investigator Jeffrey Lancet, MD, a blood cancer specialist at Moffitt, when he presented the findings at the meeting.
Presentation moderator Laura Michaelis, MD, a hematologist-oncologist at the Medical College of Wisconsin, Milwaukee, agreed.
The “strong antibody response in this group,” coupled with its high risk for severe COVID, “confirm the importance of these patients getting vaccinated,” she said.
Thirty patients with AML and 16 with MDS were included in the review. Most patients were in remission at the time of vaccination, but a third were in active treatment, including six on hypomethylating agents, six on targeted therapies, two on luspatercept, and one on lenalidomide. Thirty-two patients (69.6%) were a median of 17 months past allogeneic stem cell transplant.
Overall, 69.6% of patients developed IgG against spike proteins after the first shot and 95.7% of patients after the second dose, with a large increase in titer levels from the first to the second dose, from a mean of 315 AU/mL to 3,806.5 AU/mL following the second dose.
“Lab and clinical variables did not affect the antibody positivity rate after the second dose,” but patients on steroids and other immunosuppressants seemed less likely to respond to the first shot, Dr. Lancet said.
The study, conducted in early 2021, did not include acutely ill patients or those undergoing cheomotherapy induction and other aggressive treatments, because such patients were not being vaccinated at Moffitt during the study period.
The investigators measured anti-spike IgG by ELISA at baseline, then again about a month after the first shot and a month after the second shot.
Side effects were common and typically mild, including injection site pain, fatigue, headache, and arm swelling. Two patients with AML relapsed after vaccination.
Patients were a median of 68 years old when they were vaccinated; 58.7% were men; and almost all of the subjects were White. The median time from diagnosis to the first shot was 2 years.
The next step in the project is to study the timing of vaccination and response to it among patients on aggressive treatment and to perform neutralizing antibody assays to correlate IgG response with protection from COVID.
No funding was reported for the study. Investigators had numerous industry ties, including Dr. Lancet, a consultant for Celgene/BMS, Millenium Pharma/Takeda, AbbVie, and other firms. Dr. Michaelis didn’t have any disclosures.
aotto@mdedge.com
Factors including age, gender, race, disease status, lower-intensity active treatment, baseline neutrophil and lymphocyte counts, and past history of stem cell transplant had no effects on seroconversion in the study, which, despite its small numbers, is one of the largest series to date among patients with myeloid cancers. The findings were reported at the annual meeting of the American Society of Hematology.
COVID vaccination “appears to induce a strong antibody response” in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), unlike with B-cell malignancies. “It indicates we should be aggressive about vaccinating such patients,” said senior investigator Jeffrey Lancet, MD, a blood cancer specialist at Moffitt, when he presented the findings at the meeting.
Presentation moderator Laura Michaelis, MD, a hematologist-oncologist at the Medical College of Wisconsin, Milwaukee, agreed.
The “strong antibody response in this group,” coupled with its high risk for severe COVID, “confirm the importance of these patients getting vaccinated,” she said.
Thirty patients with AML and 16 with MDS were included in the review. Most patients were in remission at the time of vaccination, but a third were in active treatment, including six on hypomethylating agents, six on targeted therapies, two on luspatercept, and one on lenalidomide. Thirty-two patients (69.6%) were a median of 17 months past allogeneic stem cell transplant.
Overall, 69.6% of patients developed IgG against spike proteins after the first shot and 95.7% of patients after the second dose, with a large increase in titer levels from the first to the second dose, from a mean of 315 AU/mL to 3,806.5 AU/mL following the second dose.
“Lab and clinical variables did not affect the antibody positivity rate after the second dose,” but patients on steroids and other immunosuppressants seemed less likely to respond to the first shot, Dr. Lancet said.
The study, conducted in early 2021, did not include acutely ill patients or those undergoing cheomotherapy induction and other aggressive treatments, because such patients were not being vaccinated at Moffitt during the study period.
The investigators measured anti-spike IgG by ELISA at baseline, then again about a month after the first shot and a month after the second shot.
Side effects were common and typically mild, including injection site pain, fatigue, headache, and arm swelling. Two patients with AML relapsed after vaccination.
Patients were a median of 68 years old when they were vaccinated; 58.7% were men; and almost all of the subjects were White. The median time from diagnosis to the first shot was 2 years.
The next step in the project is to study the timing of vaccination and response to it among patients on aggressive treatment and to perform neutralizing antibody assays to correlate IgG response with protection from COVID.
No funding was reported for the study. Investigators had numerous industry ties, including Dr. Lancet, a consultant for Celgene/BMS, Millenium Pharma/Takeda, AbbVie, and other firms. Dr. Michaelis didn’t have any disclosures.
aotto@mdedge.com
FROM ASH 2021
‘Outstanding data’: Mosunetuzumab in r/r follicular lymphoma
An experimental bi-specific monoclonal antibody known as mosunetuzumab has induced high response rates and long-duration responses as monotherapy for patients with heavily pretreated, relapsed or refractory follicular lymphoma in a phase 2 expansion study.
At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab, reported L. Elizabeth Budde, MD, PhD, from City of Hope Comprehensive Cancer Center in Duarte, Calif.
In contrast, the complete response rate for historical controls was just 14% (P < .0001), Dr. Budde noted.
“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented.
Budde was speaking at a press briefing prior to her presentation of the data at the annual meeting of the American Society of Hematology (ASH), held in a hybrid live/virtual format.
The manufacturer, Genentech, said in a statement that based on these “highly positive results,” it plans to submit the new data to the U.S. Food and Drug Administration (FDA) in the near future for approval consideration.
If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in non-Hodgkin lymphoma, the company added.
“Outstanding” data
A lymphoma specialist who was not involved in the study told this news organization that he was favorably impressed by the findings.
“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis.
“I think as a single agent — if it does get approval — it will be a really valuable addition to the armamentarium in follicular lymphoma,” he said.
Dr. Kahl pointed to a separate phase 1b study, also presented at the meeting, suggesting that the combination of mosunetuzumab and lenalidomide (Revlimid) was safe and showed promising antitumor activity in patients with follicular lymphoma that has relapsed after at least 1 line of therapy.
“I’m very interested to see how mosunetuzumab plus lenalidomide pans out in the long run,” he said.
Study details
Mosunetuzumab engages T cells and redirects them to eliminate malignant B cells. It has the potential to be used as an off-the-shelf product, Dr. Budde said.
In the single-arm phase 2 expansion trial, Dr. Budde and colleagues enrolled 90 patients with grades 1 to 3a follicular lymphoma whose disease relapsed or was refractory to at least two prior lines of therapy, including at least one anti-CD20 monoclonal antibody, and at least one alkylating agent.
Patients were treated with step-up dosing for the first 21-day cycle to mitigate the cytokine release syndrome. They then received eight cycles if they had a complete response, and 17 cycles if they had a partial response or stable disease after eight cycles.
The primary endpoint was complete response rate by independent review, which was 60%, and the overall response rate (ORR), a secondary efficacy endpoint, was 80%.
There were no significant differences in CR or ORR rates among subgroups according to patient age, number of prior lines of therapy, relapsed or refractory disease to last prior line of therapy, double-refractory disease, or disease progression within 24 months of primary therapy.
The median duration of response among all responders was 22.8 months, with a median time to first response of 1.4 months. The 12- and 18-months event-free rates were 62% and 57%, respectively.
The safety profile was manageable, Dr. Budde said, with grade 3 or 4 drug-related adverse events occurring in about half of patients, and serious adverse events occurring in a third.
There were two deaths during the study, but neither was judged to be related to mosunetuzumab, and there were only two events leading to drug discontinuation.
Cytokine release syndrome (CRS) of any grade occurred in 40 patients (44.4%), but only 1 patient each had a grade 3 or 4 CR. The median time to CRS onset was 5.2 hours in cycle 1, and 26.6 hours in subsequent cycles. The median duration of CRS was 3 days. Ten patients had CRS managed with corticosteroids, and seven had it managed with tocilizumab.
Immune effector cell-associated neurotoxicity syndrome (ICANS) events were infrequent, and all were grade 1 or 2 in severity.
The study was supported by Genentech. Dr. Budde disclosed consulting for the company and others. Dr. Kahl has previously disclosed financial considerations with AbbVie.
A version of this article first appeared on Medscape.com.
This article was updated 12/12/21.
An experimental bi-specific monoclonal antibody known as mosunetuzumab has induced high response rates and long-duration responses as monotherapy for patients with heavily pretreated, relapsed or refractory follicular lymphoma in a phase 2 expansion study.
At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab, reported L. Elizabeth Budde, MD, PhD, from City of Hope Comprehensive Cancer Center in Duarte, Calif.
In contrast, the complete response rate for historical controls was just 14% (P < .0001), Dr. Budde noted.
“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented.
Budde was speaking at a press briefing prior to her presentation of the data at the annual meeting of the American Society of Hematology (ASH), held in a hybrid live/virtual format.
The manufacturer, Genentech, said in a statement that based on these “highly positive results,” it plans to submit the new data to the U.S. Food and Drug Administration (FDA) in the near future for approval consideration.
If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in non-Hodgkin lymphoma, the company added.
“Outstanding” data
A lymphoma specialist who was not involved in the study told this news organization that he was favorably impressed by the findings.
“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis.
“I think as a single agent — if it does get approval — it will be a really valuable addition to the armamentarium in follicular lymphoma,” he said.
Dr. Kahl pointed to a separate phase 1b study, also presented at the meeting, suggesting that the combination of mosunetuzumab and lenalidomide (Revlimid) was safe and showed promising antitumor activity in patients with follicular lymphoma that has relapsed after at least 1 line of therapy.
“I’m very interested to see how mosunetuzumab plus lenalidomide pans out in the long run,” he said.
Study details
Mosunetuzumab engages T cells and redirects them to eliminate malignant B cells. It has the potential to be used as an off-the-shelf product, Dr. Budde said.
In the single-arm phase 2 expansion trial, Dr. Budde and colleagues enrolled 90 patients with grades 1 to 3a follicular lymphoma whose disease relapsed or was refractory to at least two prior lines of therapy, including at least one anti-CD20 monoclonal antibody, and at least one alkylating agent.
Patients were treated with step-up dosing for the first 21-day cycle to mitigate the cytokine release syndrome. They then received eight cycles if they had a complete response, and 17 cycles if they had a partial response or stable disease after eight cycles.
The primary endpoint was complete response rate by independent review, which was 60%, and the overall response rate (ORR), a secondary efficacy endpoint, was 80%.
There were no significant differences in CR or ORR rates among subgroups according to patient age, number of prior lines of therapy, relapsed or refractory disease to last prior line of therapy, double-refractory disease, or disease progression within 24 months of primary therapy.
The median duration of response among all responders was 22.8 months, with a median time to first response of 1.4 months. The 12- and 18-months event-free rates were 62% and 57%, respectively.
The safety profile was manageable, Dr. Budde said, with grade 3 or 4 drug-related adverse events occurring in about half of patients, and serious adverse events occurring in a third.
There were two deaths during the study, but neither was judged to be related to mosunetuzumab, and there were only two events leading to drug discontinuation.
Cytokine release syndrome (CRS) of any grade occurred in 40 patients (44.4%), but only 1 patient each had a grade 3 or 4 CR. The median time to CRS onset was 5.2 hours in cycle 1, and 26.6 hours in subsequent cycles. The median duration of CRS was 3 days. Ten patients had CRS managed with corticosteroids, and seven had it managed with tocilizumab.
Immune effector cell-associated neurotoxicity syndrome (ICANS) events were infrequent, and all were grade 1 or 2 in severity.
The study was supported by Genentech. Dr. Budde disclosed consulting for the company and others. Dr. Kahl has previously disclosed financial considerations with AbbVie.
A version of this article first appeared on Medscape.com.
This article was updated 12/12/21.
An experimental bi-specific monoclonal antibody known as mosunetuzumab has induced high response rates and long-duration responses as monotherapy for patients with heavily pretreated, relapsed or refractory follicular lymphoma in a phase 2 expansion study.
At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab, reported L. Elizabeth Budde, MD, PhD, from City of Hope Comprehensive Cancer Center in Duarte, Calif.
In contrast, the complete response rate for historical controls was just 14% (P < .0001), Dr. Budde noted.
“We have seen deep and durable responses in heavily pretreated, high-risk relapsed/refractory follicular lymphoma patients with fixed-duration treatment. We also observed a very favorable tolerability profile, with most cytokine release syndrome confined to cycle 1 and low grade, and treatment administration is without mandatory hospitalization,” she commented.
Budde was speaking at a press briefing prior to her presentation of the data at the annual meeting of the American Society of Hematology (ASH), held in a hybrid live/virtual format.
The manufacturer, Genentech, said in a statement that based on these “highly positive results,” it plans to submit the new data to the U.S. Food and Drug Administration (FDA) in the near future for approval consideration.
If approved, mosunetuzumab has the potential to be a first-in-class CD20xCD3 T-cell engaging bispecific antibody in non-Hodgkin lymphoma, the company added.
“Outstanding” data
A lymphoma specialist who was not involved in the study told this news organization that he was favorably impressed by the findings.
“To me, the single-agent data looks really outstanding, with a response rate of 80%, a complete response rate of 60%, and a median duration of response of 23 months, and really very acceptable rates of cytokine release syndrome,” commented Brad S. Kahl, MD, from the Siteman Cancer Center and Washington University School of Medicine in St. Louis.
“I think as a single agent — if it does get approval — it will be a really valuable addition to the armamentarium in follicular lymphoma,” he said.
Dr. Kahl pointed to a separate phase 1b study, also presented at the meeting, suggesting that the combination of mosunetuzumab and lenalidomide (Revlimid) was safe and showed promising antitumor activity in patients with follicular lymphoma that has relapsed after at least 1 line of therapy.
“I’m very interested to see how mosunetuzumab plus lenalidomide pans out in the long run,” he said.
Study details
Mosunetuzumab engages T cells and redirects them to eliminate malignant B cells. It has the potential to be used as an off-the-shelf product, Dr. Budde said.
In the single-arm phase 2 expansion trial, Dr. Budde and colleagues enrolled 90 patients with grades 1 to 3a follicular lymphoma whose disease relapsed or was refractory to at least two prior lines of therapy, including at least one anti-CD20 monoclonal antibody, and at least one alkylating agent.
Patients were treated with step-up dosing for the first 21-day cycle to mitigate the cytokine release syndrome. They then received eight cycles if they had a complete response, and 17 cycles if they had a partial response or stable disease after eight cycles.
The primary endpoint was complete response rate by independent review, which was 60%, and the overall response rate (ORR), a secondary efficacy endpoint, was 80%.
There were no significant differences in CR or ORR rates among subgroups according to patient age, number of prior lines of therapy, relapsed or refractory disease to last prior line of therapy, double-refractory disease, or disease progression within 24 months of primary therapy.
The median duration of response among all responders was 22.8 months, with a median time to first response of 1.4 months. The 12- and 18-months event-free rates were 62% and 57%, respectively.
The safety profile was manageable, Dr. Budde said, with grade 3 or 4 drug-related adverse events occurring in about half of patients, and serious adverse events occurring in a third.
There were two deaths during the study, but neither was judged to be related to mosunetuzumab, and there were only two events leading to drug discontinuation.
Cytokine release syndrome (CRS) of any grade occurred in 40 patients (44.4%), but only 1 patient each had a grade 3 or 4 CR. The median time to CRS onset was 5.2 hours in cycle 1, and 26.6 hours in subsequent cycles. The median duration of CRS was 3 days. Ten patients had CRS managed with corticosteroids, and seven had it managed with tocilizumab.
Immune effector cell-associated neurotoxicity syndrome (ICANS) events were infrequent, and all were grade 1 or 2 in severity.
The study was supported by Genentech. Dr. Budde disclosed consulting for the company and others. Dr. Kahl has previously disclosed financial considerations with AbbVie.
A version of this article first appeared on Medscape.com.
This article was updated 12/12/21.
AT ASH 2021
For leukemias, COVID-19 death risks tied to poor prognoses, ICU deferrals
, results of an American Society of Hematology (ASH) COVID-19 registry study suggest.
Rates of severe COVID-19 were significantly higher among patients who had active disease or neutropenia at the time of their COVID-19 diagnosis. Mortality related to COVID-19 was linked to neutropenia, primary disease prognosis of less than 6 months, and deferral of recommended ICU care, study results show.
By contrast, mortality was not associated with active primary disease or its treatment, according to researcher Pinkal Desai, MD, MPH.
Taken together, these findings provide preliminary evidence to support the use of aggressive supportive treatment of COVID-19 in patients with acute leukemias and myelodysplastic syndromes, said Dr. Desai, a hematologist-oncologist with Weill Cornell Medicine and NewYork-Presbyterian in New York.
“If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate, regardless of remission status, given the results of our study,” Dr. Desai said in a press conference during the annual meeting of the American Society of Hematology.
In non-cancer patient populations, advanced age and cytopenias have been associated with mortality related to COVID-19, Dr. Desai said. Likewise, patients with acute leukemias and myelodysplastic syndrome are generally older and have disease- or treatment-related cytopenias, which might affect the severity of and mortality from COVID-19, she added.
With that concern in mind, Dr. Desai and co-investigators looked at predictors of severe COVID-19 disease and death among patients in the ASH Research Collaborative (ASH RC) COVID-19 Registry for Hematology.
This registry was started in the early days of the pandemic to provide real-time observational COVID-19 data to clinicians, according to an ASH news release.
The analysis by Dr. Desai and co-authors included 257 patients with COVID-19 as determined by their physician, including 135 with a primary diagnosis of acute myeloid leukemia, 82 with acute lymphocytic leukemia, and 40 with myelodysplastic syndromes. Sixty percent of the patients were hospitalized due to COVID-19.
At the time of COVID-19 diagnosis, 46% of patients were in remission, and 44% had active disease, according to the report.
Both neutropenia and active disease status at COVID-19 diagnosis were linked to severe COVID-19, defined as ICU admission due to a COVID-19-related reason, according to results of multivariable analysis. Among patients with severe COVID-19, 67% had active disease, meaning just 33% were in remission, Dr. Desai noted.
In multivariable analysis, two factors were significantly associated with mortality, she added: having an estimated pre-COVID-19 prognosis from the primary disease of less than 6 months, and deferral of ICU care when it was recommended to the patient.
Mortality was 21% overall, higher than would be expected in a non-cancer population, Dr. Desai said. For patients with COVID-19 requiring hospitalization, the mortality rate was 34% and for those patients who did go to the ICU, the mortality rate was 68%.
By contrast, there was no significant association between mortality and active disease as compared to disease in remission, Dr. Desai noted in her presentation. Likewise, mortality was not associated with active treatment at the time of COVID-19 diagnosis as compared to no treatment.
Gwen Nichols, MD, executive vice president and chief medical officer of the Leukemia & Lymphoma Society, New York, said those are reassuring data for patients with acute leukemias and myelodysplastic syndromes and their healthcare providers.
“From our point of view, it helps us say, ‘do not stop your treatment because of worries about COVID-19—it’s more important that you treat your cancer,” Dr. Nichols said in an interview. “We now know we can help people through COVID-19, and I think this is just really important data to back that up,” she added.
Dr. Desai provided disclosures related to Agios, Kura Oncology, and Bristol Myers Squibb (consultancy), and to Janssen R&D and Astex (research funding).
, results of an American Society of Hematology (ASH) COVID-19 registry study suggest.
Rates of severe COVID-19 were significantly higher among patients who had active disease or neutropenia at the time of their COVID-19 diagnosis. Mortality related to COVID-19 was linked to neutropenia, primary disease prognosis of less than 6 months, and deferral of recommended ICU care, study results show.
By contrast, mortality was not associated with active primary disease or its treatment, according to researcher Pinkal Desai, MD, MPH.
Taken together, these findings provide preliminary evidence to support the use of aggressive supportive treatment of COVID-19 in patients with acute leukemias and myelodysplastic syndromes, said Dr. Desai, a hematologist-oncologist with Weill Cornell Medicine and NewYork-Presbyterian in New York.
“If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate, regardless of remission status, given the results of our study,” Dr. Desai said in a press conference during the annual meeting of the American Society of Hematology.
In non-cancer patient populations, advanced age and cytopenias have been associated with mortality related to COVID-19, Dr. Desai said. Likewise, patients with acute leukemias and myelodysplastic syndrome are generally older and have disease- or treatment-related cytopenias, which might affect the severity of and mortality from COVID-19, she added.
With that concern in mind, Dr. Desai and co-investigators looked at predictors of severe COVID-19 disease and death among patients in the ASH Research Collaborative (ASH RC) COVID-19 Registry for Hematology.
This registry was started in the early days of the pandemic to provide real-time observational COVID-19 data to clinicians, according to an ASH news release.
The analysis by Dr. Desai and co-authors included 257 patients with COVID-19 as determined by their physician, including 135 with a primary diagnosis of acute myeloid leukemia, 82 with acute lymphocytic leukemia, and 40 with myelodysplastic syndromes. Sixty percent of the patients were hospitalized due to COVID-19.
At the time of COVID-19 diagnosis, 46% of patients were in remission, and 44% had active disease, according to the report.
Both neutropenia and active disease status at COVID-19 diagnosis were linked to severe COVID-19, defined as ICU admission due to a COVID-19-related reason, according to results of multivariable analysis. Among patients with severe COVID-19, 67% had active disease, meaning just 33% were in remission, Dr. Desai noted.
In multivariable analysis, two factors were significantly associated with mortality, she added: having an estimated pre-COVID-19 prognosis from the primary disease of less than 6 months, and deferral of ICU care when it was recommended to the patient.
Mortality was 21% overall, higher than would be expected in a non-cancer population, Dr. Desai said. For patients with COVID-19 requiring hospitalization, the mortality rate was 34% and for those patients who did go to the ICU, the mortality rate was 68%.
By contrast, there was no significant association between mortality and active disease as compared to disease in remission, Dr. Desai noted in her presentation. Likewise, mortality was not associated with active treatment at the time of COVID-19 diagnosis as compared to no treatment.
Gwen Nichols, MD, executive vice president and chief medical officer of the Leukemia & Lymphoma Society, New York, said those are reassuring data for patients with acute leukemias and myelodysplastic syndromes and their healthcare providers.
“From our point of view, it helps us say, ‘do not stop your treatment because of worries about COVID-19—it’s more important that you treat your cancer,” Dr. Nichols said in an interview. “We now know we can help people through COVID-19, and I think this is just really important data to back that up,” she added.
Dr. Desai provided disclosures related to Agios, Kura Oncology, and Bristol Myers Squibb (consultancy), and to Janssen R&D and Astex (research funding).
, results of an American Society of Hematology (ASH) COVID-19 registry study suggest.
Rates of severe COVID-19 were significantly higher among patients who had active disease or neutropenia at the time of their COVID-19 diagnosis. Mortality related to COVID-19 was linked to neutropenia, primary disease prognosis of less than 6 months, and deferral of recommended ICU care, study results show.
By contrast, mortality was not associated with active primary disease or its treatment, according to researcher Pinkal Desai, MD, MPH.
Taken together, these findings provide preliminary evidence to support the use of aggressive supportive treatment of COVID-19 in patients with acute leukemias and myelodysplastic syndromes, said Dr. Desai, a hematologist-oncologist with Weill Cornell Medicine and NewYork-Presbyterian in New York.
“If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate, regardless of remission status, given the results of our study,” Dr. Desai said in a press conference during the annual meeting of the American Society of Hematology.
In non-cancer patient populations, advanced age and cytopenias have been associated with mortality related to COVID-19, Dr. Desai said. Likewise, patients with acute leukemias and myelodysplastic syndrome are generally older and have disease- or treatment-related cytopenias, which might affect the severity of and mortality from COVID-19, she added.
With that concern in mind, Dr. Desai and co-investigators looked at predictors of severe COVID-19 disease and death among patients in the ASH Research Collaborative (ASH RC) COVID-19 Registry for Hematology.
This registry was started in the early days of the pandemic to provide real-time observational COVID-19 data to clinicians, according to an ASH news release.
The analysis by Dr. Desai and co-authors included 257 patients with COVID-19 as determined by their physician, including 135 with a primary diagnosis of acute myeloid leukemia, 82 with acute lymphocytic leukemia, and 40 with myelodysplastic syndromes. Sixty percent of the patients were hospitalized due to COVID-19.
At the time of COVID-19 diagnosis, 46% of patients were in remission, and 44% had active disease, according to the report.
Both neutropenia and active disease status at COVID-19 diagnosis were linked to severe COVID-19, defined as ICU admission due to a COVID-19-related reason, according to results of multivariable analysis. Among patients with severe COVID-19, 67% had active disease, meaning just 33% were in remission, Dr. Desai noted.
In multivariable analysis, two factors were significantly associated with mortality, she added: having an estimated pre-COVID-19 prognosis from the primary disease of less than 6 months, and deferral of ICU care when it was recommended to the patient.
Mortality was 21% overall, higher than would be expected in a non-cancer population, Dr. Desai said. For patients with COVID-19 requiring hospitalization, the mortality rate was 34% and for those patients who did go to the ICU, the mortality rate was 68%.
By contrast, there was no significant association between mortality and active disease as compared to disease in remission, Dr. Desai noted in her presentation. Likewise, mortality was not associated with active treatment at the time of COVID-19 diagnosis as compared to no treatment.
Gwen Nichols, MD, executive vice president and chief medical officer of the Leukemia & Lymphoma Society, New York, said those are reassuring data for patients with acute leukemias and myelodysplastic syndromes and their healthcare providers.
“From our point of view, it helps us say, ‘do not stop your treatment because of worries about COVID-19—it’s more important that you treat your cancer,” Dr. Nichols said in an interview. “We now know we can help people through COVID-19, and I think this is just really important data to back that up,” she added.
Dr. Desai provided disclosures related to Agios, Kura Oncology, and Bristol Myers Squibb (consultancy), and to Janssen R&D and Astex (research funding).
FROM ASH 2021
Beta-thalassemia gene therapy achieves lasting transfusion independence
, an investigator reported at the annual meeting of the American Society of Hematology.
Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.
In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.
Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.
“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.
This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.
“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.
Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.
“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.
Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.
With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.
Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.
At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.
A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.
Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.
“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.
Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.
Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.
The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.
Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.
Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.
“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.
Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
, an investigator reported at the annual meeting of the American Society of Hematology.
Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.
In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.
Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.
“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.
This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.
“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.
Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.
“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.
Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.
With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.
Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.
At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.
A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.
Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.
“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.
Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.
Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.
The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.
Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.
Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.
“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.
Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
, an investigator reported at the annual meeting of the American Society of Hematology.
Among patients who received betibeglogene autotemcel (beti-cel) in a phase 3 trial and enrolled in a long-term follow-up study, nearly 90% achieved durable transfusion independence, according to Alexis A. Thompson, MD, MPH, of the hematology section at the Ann & Robert H. Lurie Children’s Hospital of Chicago.
The median duration of ongoing transfusion independence was nearly 3 years as of this report, which Dr. Thompson described in a press conference at the meeting.
In a subanalysis of this international study, Dr. Thompson and co-investigators reported that in patients who achieve transfusion independence, chelation reduced iron, and iron markers stabilized even after chelation was stopped.
Beyond 2 years post-infusion, no adverse events related to the drug product were seen. This suggested that the therapy has a favorable long-term safety profile, according to Dr. Thompson.
“At this point, we believe that beti-cel is potentially curative for patients with TDT [transfusion-dependent beta-thalassemia],” Dr. Thompson said in the press conference.
This study answers one of the major outstanding questions about beti-cel and iron metabolism, according to Arielle L. Langer, MD, MPH, an instructor in medicine at Harvard Medical School and attending physician for adult thalassemia patients at Brigham and Women’s and Dana Farber Cancer Institute, both in Boston.
“Seeing the restoration of iron metabolism, it really takes us a step closer to really thinking the term ‘cure’ might truly apply,” Dr. Langer said in an interview.
Dr. Langer said she looks forward to “very long-term outcomes” of beti-cel-treated patients to see whether endocrinopathies and other long-term sequelae of TDT are also abated.
“This [study] is a great intermediate point, but really, when we think about how thalassemia harms and kills our patients, we really sometimes measure that in decades,” she said.
Beta-thalassemia is caused by mutations in the beta-globin gene, resulting in reduced levels of hemoglobin. Patients with TDT, the most serious form of the disease, have severe anemia and are often dependent on red blood cell transfusions from infancy onward, Dr. Thompson said.
With chronic transfusions needed to maintain hemoglobin levels, TDT patients inevitably experience iron overload, which can lead to organ damage and can be fatal. Consequently, patients will require lifelong iron chelation therapy, she added.
Beti-cel, an investigational ex vivo gene addition therapy currently under review by the U.S. Food and Drug Administration, involves adding functional copies of a modified form of the beta-globin gene into a patient’s own hematopoietic stem cells. Once those cells are reinfused, patients may produce adult hemoglobin at levels that eliminate the need for transfusions, according to Dr. Thompson.
At the meeting, Dr. Thompson reported on patients from two phase 1/2 and two phase 3 beti-cel clinical trials who subsequently enrolled in LTF-303, a 13-year follow-up study of the gene therapy’s safety and efficacy.
A total of 57 patients were included in this report, making it the largest gene therapy program to date in any blood disorder, according to Dr. Thompson. Before receiving beti-cel, the patients, who had a broad range of thalassemia genotypes, were receiving between 10 and almost 40 red blood cell transfusions per year, she reported.
Patients ranged in age from 5 to 35 years. The median age in the phase 1/2 studies was 20 years, while in the phase 3 studies it was 15 years.
“The early experience in the phase 1/2 trials allowed us to be more comfortable with enrolling more children, and that has actually helped us to understand safety and efficacy and children in the phase 3 setting,” Dr. Thompson said.
Fertility preservation measures had been undertaken by about 59% of patients from the phase 1/2 studies and 71% of patients from the phase 3 studies, the data show.
Among patients from the phase 3 beti-cel studies who could be evaluated, 31 out of 35 (or 89%) achieved durable transfusion independence, according to the investigator.
The median duration of ongoing transfusion independence was 32 months, with a range of about 18 to 49 months, she added.
Dr. Thompson also reported a subanalysis intended to assess iron status in 16 patients who restarted and then stopped chelation. That subanalysis demonstrated iron reduction in response to chelation, and then stabilization of iron markers after chelation was stopped. Post-gene therapy chelation led to reductions in liver iron concentration and serum ferritin that remained relatively stable after chelation was stopped, she said.
Serious adverse events occurred in eight patients in the long-term follow-up study. However, adverse events related to beti-cel have been absent beyond 2 years post-infusion, according to Dr. Thompson, who added that there have been no reported cases of replication-competent lentivirus, no clonal expansion, no insertional oncogenesis, and no malignancies observed.
“Very reassuringly, there have been 2 male patients, one of whom underwent fertility preservation, who report having healthy children with their partners,” she added.
Dr. Thompson provided disclosures related to Baxalta, Biomarin, bluebird bio, Inc., Celgene/BMS, CRISPR Therapeutics, Vertex, Editas, Graphite Bio, Novartis, Agios, Beam, and Global Blood Therapeutics.
FROM ASH 2021
‘Remarkable’ results with CAR T cells could make chemo obsolete
ATLANTA — Chimeric antigen receptor, results of the phase 3 ZUMA-7 and TRANSFORM trials suggest.
In the ZUMA-7 trial, at a median follow-up of 24.9 months, patients randomly assigned to receive CAR T-cell therapy with axicabtagene ciloleucel, or axi-cell (Yescarta) had a median event-free survival (EFS) of 8.3 months, compared with 2 months for patients randomly assigned to standard-of-care chemoimmunotherapy, reported Frederick L. Locke, MD, from the Moffitt Cancer Center in Tampa, Fla.
In TRANSFORM, comparing the CAR T construct lisocabtagene maraleucel, or liso-cel (Breyanzi) with standard-of-care second-line chemotherapy, median EFS was 10.1 months with liso-cel, compared with 2.3 months with standard of care, reported Manali Kamdar, MD, from the University of Colorado Cancer Center in Aurora.
The trials differed slightly in eligibility criteria and other details, but their overall results show great promise for improving second-line therapy for patients with relapsed or refractory LBCL, commented Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer in Vancouver, Canada.
“It’s really remarkable that the results are so far in favor of the CAR T-cell therapy that I think it’s inevitable that this will become the standard of care,” Dr. Sehn commented. She was not an investigator in either of the two trials.
Dr. Sehn was speaking at a press briefing here during the annual meeting of the American Society of Hematology. The new data from the two studies were presented at oral sessions, and the results from ZUMA-7 were also simultaneously published in the New England Journal of Medicine.
“For somebody who treats patients with large B-cell lymphoma like I do, it’s incredibly frustrating when patients fail frontline therapy,” Dr. Sehn said. “We come into the second line with more chemotherapy and at higher doses to try and slam things down hard. Particularly for the patients who were enrolled in these studies, which were the worst of the worst — the patients who are either refractory to chemotherapy or relapsed relatively early, within 1 year — it’s not surprising that coming in with a novel approach and a cellular therapy that has a proven curative capacity may have outperformed coming in with more chemotherapy.”
In an interview with this news organization, Dr. Locke said that, based on the findings of the ZUMA-7 trial that he presented, it’s likely that chemotherapy in the second-line setting for relapsed/refractory LBCL will largely fall by the wayside.
The first question is to identify the patients who can tolerate CAR T-cell therapy. “We need to refer these patients to a CAR T-cell center to make that decision. That decision really can’t be made in the local oncologist’s office,” he said. “That being said, there are patients who need urgent therapy, and they may need to get second-line chemotherapy right away.”
“What we know with CAR T cells is that older patients and patients with comorbidities can get these therapies safely, so to me there is no obvious patient who can’t get CAR T-cell therapy,” he added.
Also at the briefing, Dr. Kamdar, who presented the TRANSFORM trial results, remarked that “in my opinion, this is a breakthrough therapy, which has shown superiority over standard of care, in terms of not just efficacy but also an extremely favorable safety profile,” she said at a briefing.
For patients with LBCL for whom first-line therapy has failed, chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) has been the standard of care, but only about 25% of patients who are candidates for ASCT achieve durable remissions, Dr. Kamdar noted.
Both ZUMA-7 and TRANSFORM were designed to test whether moving CAR T-cell therapy forward into the second line could improve outcomes.
ZUMA-7 results
THE ZUMA-7 trial randomly assigned 180 patients to receive CAR T-cell therapy with axi-cell and 179 patients to standard of care. This consisted of two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, with patients who had a complete or partial response going onto ASCT.
As noted, the primary endpoint of EFS according to blinded central review favored axi-cel, with 24-month event-free survival rates of 41% vs. 16% for standard of care. The difference translated into a hazard ratio (HR) for progression or death of 0.40 (P < .001).
In all, 65% of patients had a complete response (CR) to axi-cel, compared with 32% with standard of care. The respective overall response rates were 83% and 50% (P < .001).
Dr. Locke pointed out that 94% of the patients assigned to axi-cel received definitive therapy, compared with the 36% of patients in the standard-of-care arm who went on to ASCT.
In an interim analysis, 2-year estimated overall survival was 61% with axi-cel vs. 52% with standard of care, although this difference was not statistically significant.
Median overall survival was not reached with axi-cel, compared with 35.1 months with standard-of-care.
Grade 3 or higher adverse events occurred in 91% of patients with CAR T, and 83% with the standard of care. In the axi-cel arm, 6% of patients had grade 3 or higher cytokine release syndrome (CRS), and 21% had grade 3 or higher neurologic events, although there were no deaths related to CRS or neurologic events.
TRANSFORM results
The TRANSFORM trial had broader eligibility criteria than ZUMA-7, including patients who had diffuse LBCL not otherwise specified (de novo or transformed from indolent NHL), high-grade BCL (double- or triple-hit) with DLBCL histology, follicular lymphoma grade 3B, primary mediastinal LBCL, or T-cell/histocyte-rich LBCL.
A total of 184 patients were randomly assigned, 92 in each group, to receive either liso-cel or standard-of-care. Patients assigned to liso-cel were allowed to have bridging therapy, and crossover to liso-cel was allowed for patients assigned to standard of care who either did not have a response by week 9 after randomization, had disease progression at any time, or started a new antineoplastic therapy after ASCT.
As noted before, the primary endpoint of EFS significantly favored CAR T-cell therapy, with a hazard ratio of 0.349 (P < .0001).
The EFS rates at 6 months were 63.3% with liso-cel vs 33.4% with standard of care, and the EFS rates at 12 months were 44.5% vs. 23.7%, respectively.
“Overall survival data were still immature at the time of this analysis, but show a trend favoring liso-cel, despite crossover,” Dr. Kamdar said.
Grade 3 or higher adverse events (AEs) occurred in 92% of patients on liso-cell and 87% of patients on standard of care. There was one treatment-related death in the liso-cel arm, and two in the standard of care arm, both from grade 3 or higher AEs. Neutropenia, anemia, and thrombocytopenia were the most common treatment-emergent AEs in each group.
ZUMA-7 is supported by Kite. Dr. Locke disclosed serving as a scientific advisor to Kite and relationships with other companies. TRANSFORM is supported by Celgene (BMS). Dr. Kamdar disclosed consultancy fees from BMS and others.
A version of this article first appeared on Medscape.com.
ATLANTA — Chimeric antigen receptor, results of the phase 3 ZUMA-7 and TRANSFORM trials suggest.
In the ZUMA-7 trial, at a median follow-up of 24.9 months, patients randomly assigned to receive CAR T-cell therapy with axicabtagene ciloleucel, or axi-cell (Yescarta) had a median event-free survival (EFS) of 8.3 months, compared with 2 months for patients randomly assigned to standard-of-care chemoimmunotherapy, reported Frederick L. Locke, MD, from the Moffitt Cancer Center in Tampa, Fla.
In TRANSFORM, comparing the CAR T construct lisocabtagene maraleucel, or liso-cel (Breyanzi) with standard-of-care second-line chemotherapy, median EFS was 10.1 months with liso-cel, compared with 2.3 months with standard of care, reported Manali Kamdar, MD, from the University of Colorado Cancer Center in Aurora.
The trials differed slightly in eligibility criteria and other details, but their overall results show great promise for improving second-line therapy for patients with relapsed or refractory LBCL, commented Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer in Vancouver, Canada.
“It’s really remarkable that the results are so far in favor of the CAR T-cell therapy that I think it’s inevitable that this will become the standard of care,” Dr. Sehn commented. She was not an investigator in either of the two trials.
Dr. Sehn was speaking at a press briefing here during the annual meeting of the American Society of Hematology. The new data from the two studies were presented at oral sessions, and the results from ZUMA-7 were also simultaneously published in the New England Journal of Medicine.
“For somebody who treats patients with large B-cell lymphoma like I do, it’s incredibly frustrating when patients fail frontline therapy,” Dr. Sehn said. “We come into the second line with more chemotherapy and at higher doses to try and slam things down hard. Particularly for the patients who were enrolled in these studies, which were the worst of the worst — the patients who are either refractory to chemotherapy or relapsed relatively early, within 1 year — it’s not surprising that coming in with a novel approach and a cellular therapy that has a proven curative capacity may have outperformed coming in with more chemotherapy.”
In an interview with this news organization, Dr. Locke said that, based on the findings of the ZUMA-7 trial that he presented, it’s likely that chemotherapy in the second-line setting for relapsed/refractory LBCL will largely fall by the wayside.
The first question is to identify the patients who can tolerate CAR T-cell therapy. “We need to refer these patients to a CAR T-cell center to make that decision. That decision really can’t be made in the local oncologist’s office,” he said. “That being said, there are patients who need urgent therapy, and they may need to get second-line chemotherapy right away.”
“What we know with CAR T cells is that older patients and patients with comorbidities can get these therapies safely, so to me there is no obvious patient who can’t get CAR T-cell therapy,” he added.
Also at the briefing, Dr. Kamdar, who presented the TRANSFORM trial results, remarked that “in my opinion, this is a breakthrough therapy, which has shown superiority over standard of care, in terms of not just efficacy but also an extremely favorable safety profile,” she said at a briefing.
For patients with LBCL for whom first-line therapy has failed, chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) has been the standard of care, but only about 25% of patients who are candidates for ASCT achieve durable remissions, Dr. Kamdar noted.
Both ZUMA-7 and TRANSFORM were designed to test whether moving CAR T-cell therapy forward into the second line could improve outcomes.
ZUMA-7 results
THE ZUMA-7 trial randomly assigned 180 patients to receive CAR T-cell therapy with axi-cell and 179 patients to standard of care. This consisted of two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, with patients who had a complete or partial response going onto ASCT.
As noted, the primary endpoint of EFS according to blinded central review favored axi-cel, with 24-month event-free survival rates of 41% vs. 16% for standard of care. The difference translated into a hazard ratio (HR) for progression or death of 0.40 (P < .001).
In all, 65% of patients had a complete response (CR) to axi-cel, compared with 32% with standard of care. The respective overall response rates were 83% and 50% (P < .001).
Dr. Locke pointed out that 94% of the patients assigned to axi-cel received definitive therapy, compared with the 36% of patients in the standard-of-care arm who went on to ASCT.
In an interim analysis, 2-year estimated overall survival was 61% with axi-cel vs. 52% with standard of care, although this difference was not statistically significant.
Median overall survival was not reached with axi-cel, compared with 35.1 months with standard-of-care.
Grade 3 or higher adverse events occurred in 91% of patients with CAR T, and 83% with the standard of care. In the axi-cel arm, 6% of patients had grade 3 or higher cytokine release syndrome (CRS), and 21% had grade 3 or higher neurologic events, although there were no deaths related to CRS or neurologic events.
TRANSFORM results
The TRANSFORM trial had broader eligibility criteria than ZUMA-7, including patients who had diffuse LBCL not otherwise specified (de novo or transformed from indolent NHL), high-grade BCL (double- or triple-hit) with DLBCL histology, follicular lymphoma grade 3B, primary mediastinal LBCL, or T-cell/histocyte-rich LBCL.
A total of 184 patients were randomly assigned, 92 in each group, to receive either liso-cel or standard-of-care. Patients assigned to liso-cel were allowed to have bridging therapy, and crossover to liso-cel was allowed for patients assigned to standard of care who either did not have a response by week 9 after randomization, had disease progression at any time, or started a new antineoplastic therapy after ASCT.
As noted before, the primary endpoint of EFS significantly favored CAR T-cell therapy, with a hazard ratio of 0.349 (P < .0001).
The EFS rates at 6 months were 63.3% with liso-cel vs 33.4% with standard of care, and the EFS rates at 12 months were 44.5% vs. 23.7%, respectively.
“Overall survival data were still immature at the time of this analysis, but show a trend favoring liso-cel, despite crossover,” Dr. Kamdar said.
Grade 3 or higher adverse events (AEs) occurred in 92% of patients on liso-cell and 87% of patients on standard of care. There was one treatment-related death in the liso-cel arm, and two in the standard of care arm, both from grade 3 or higher AEs. Neutropenia, anemia, and thrombocytopenia were the most common treatment-emergent AEs in each group.
ZUMA-7 is supported by Kite. Dr. Locke disclosed serving as a scientific advisor to Kite and relationships with other companies. TRANSFORM is supported by Celgene (BMS). Dr. Kamdar disclosed consultancy fees from BMS and others.
A version of this article first appeared on Medscape.com.
ATLANTA — Chimeric antigen receptor, results of the phase 3 ZUMA-7 and TRANSFORM trials suggest.
In the ZUMA-7 trial, at a median follow-up of 24.9 months, patients randomly assigned to receive CAR T-cell therapy with axicabtagene ciloleucel, or axi-cell (Yescarta) had a median event-free survival (EFS) of 8.3 months, compared with 2 months for patients randomly assigned to standard-of-care chemoimmunotherapy, reported Frederick L. Locke, MD, from the Moffitt Cancer Center in Tampa, Fla.
In TRANSFORM, comparing the CAR T construct lisocabtagene maraleucel, or liso-cel (Breyanzi) with standard-of-care second-line chemotherapy, median EFS was 10.1 months with liso-cel, compared with 2.3 months with standard of care, reported Manali Kamdar, MD, from the University of Colorado Cancer Center in Aurora.
The trials differed slightly in eligibility criteria and other details, but their overall results show great promise for improving second-line therapy for patients with relapsed or refractory LBCL, commented Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer in Vancouver, Canada.
“It’s really remarkable that the results are so far in favor of the CAR T-cell therapy that I think it’s inevitable that this will become the standard of care,” Dr. Sehn commented. She was not an investigator in either of the two trials.
Dr. Sehn was speaking at a press briefing here during the annual meeting of the American Society of Hematology. The new data from the two studies were presented at oral sessions, and the results from ZUMA-7 were also simultaneously published in the New England Journal of Medicine.
“For somebody who treats patients with large B-cell lymphoma like I do, it’s incredibly frustrating when patients fail frontline therapy,” Dr. Sehn said. “We come into the second line with more chemotherapy and at higher doses to try and slam things down hard. Particularly for the patients who were enrolled in these studies, which were the worst of the worst — the patients who are either refractory to chemotherapy or relapsed relatively early, within 1 year — it’s not surprising that coming in with a novel approach and a cellular therapy that has a proven curative capacity may have outperformed coming in with more chemotherapy.”
In an interview with this news organization, Dr. Locke said that, based on the findings of the ZUMA-7 trial that he presented, it’s likely that chemotherapy in the second-line setting for relapsed/refractory LBCL will largely fall by the wayside.
The first question is to identify the patients who can tolerate CAR T-cell therapy. “We need to refer these patients to a CAR T-cell center to make that decision. That decision really can’t be made in the local oncologist’s office,” he said. “That being said, there are patients who need urgent therapy, and they may need to get second-line chemotherapy right away.”
“What we know with CAR T cells is that older patients and patients with comorbidities can get these therapies safely, so to me there is no obvious patient who can’t get CAR T-cell therapy,” he added.
Also at the briefing, Dr. Kamdar, who presented the TRANSFORM trial results, remarked that “in my opinion, this is a breakthrough therapy, which has shown superiority over standard of care, in terms of not just efficacy but also an extremely favorable safety profile,” she said at a briefing.
For patients with LBCL for whom first-line therapy has failed, chemoimmunotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) has been the standard of care, but only about 25% of patients who are candidates for ASCT achieve durable remissions, Dr. Kamdar noted.
Both ZUMA-7 and TRANSFORM were designed to test whether moving CAR T-cell therapy forward into the second line could improve outcomes.
ZUMA-7 results
THE ZUMA-7 trial randomly assigned 180 patients to receive CAR T-cell therapy with axi-cell and 179 patients to standard of care. This consisted of two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, with patients who had a complete or partial response going onto ASCT.
As noted, the primary endpoint of EFS according to blinded central review favored axi-cel, with 24-month event-free survival rates of 41% vs. 16% for standard of care. The difference translated into a hazard ratio (HR) for progression or death of 0.40 (P < .001).
In all, 65% of patients had a complete response (CR) to axi-cel, compared with 32% with standard of care. The respective overall response rates were 83% and 50% (P < .001).
Dr. Locke pointed out that 94% of the patients assigned to axi-cel received definitive therapy, compared with the 36% of patients in the standard-of-care arm who went on to ASCT.
In an interim analysis, 2-year estimated overall survival was 61% with axi-cel vs. 52% with standard of care, although this difference was not statistically significant.
Median overall survival was not reached with axi-cel, compared with 35.1 months with standard-of-care.
Grade 3 or higher adverse events occurred in 91% of patients with CAR T, and 83% with the standard of care. In the axi-cel arm, 6% of patients had grade 3 or higher cytokine release syndrome (CRS), and 21% had grade 3 or higher neurologic events, although there were no deaths related to CRS or neurologic events.
TRANSFORM results
The TRANSFORM trial had broader eligibility criteria than ZUMA-7, including patients who had diffuse LBCL not otherwise specified (de novo or transformed from indolent NHL), high-grade BCL (double- or triple-hit) with DLBCL histology, follicular lymphoma grade 3B, primary mediastinal LBCL, or T-cell/histocyte-rich LBCL.
A total of 184 patients were randomly assigned, 92 in each group, to receive either liso-cel or standard-of-care. Patients assigned to liso-cel were allowed to have bridging therapy, and crossover to liso-cel was allowed for patients assigned to standard of care who either did not have a response by week 9 after randomization, had disease progression at any time, or started a new antineoplastic therapy after ASCT.
As noted before, the primary endpoint of EFS significantly favored CAR T-cell therapy, with a hazard ratio of 0.349 (P < .0001).
The EFS rates at 6 months were 63.3% with liso-cel vs 33.4% with standard of care, and the EFS rates at 12 months were 44.5% vs. 23.7%, respectively.
“Overall survival data were still immature at the time of this analysis, but show a trend favoring liso-cel, despite crossover,” Dr. Kamdar said.
Grade 3 or higher adverse events (AEs) occurred in 92% of patients on liso-cell and 87% of patients on standard of care. There was one treatment-related death in the liso-cel arm, and two in the standard of care arm, both from grade 3 or higher AEs. Neutropenia, anemia, and thrombocytopenia were the most common treatment-emergent AEs in each group.
ZUMA-7 is supported by Kite. Dr. Locke disclosed serving as a scientific advisor to Kite and relationships with other companies. TRANSFORM is supported by Celgene (BMS). Dr. Kamdar disclosed consultancy fees from BMS and others.
A version of this article first appeared on Medscape.com.
AT ASH 2021
Liver cancer risk lingers even after HCV eradication
Although the risk for liver cancer diminishes for patients with hepatitis C virus (HCV) infections for whom the virus is eliminated with direct-acting antiviral (DAA) drugs, these patients are not out of the woods, and those who do not have a sustained viral response (SVR) are at substantially higher risk of developing hepatocellular carcinoma (HCC), results of a large study show.
Among the patients with liver cirrhosis from HCV infections treated at 30 centers in Italy, a large percentage had an SVR after treatment with DAA drugs. Only a small percentage of this group subsequently developed HCC.
In contrast, not having an SVR was associated with a more than sevenfold higher risk for liver cancer, said Loreta A. Kondili, MD, PhD, from the Center for Global Health at the Istituto Superiore di Sanità, Rome, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.
“Failure to achieve SVR after DAA treatment is strongly associated with the probability of HCC development. Older age, [HCV] genotype 3, and low platelet counts and albumin levels are independent factors of HCC development despite viral eradication,” she said.
Cohort study
The study findings come from the PITER Cohort Study, a prospective, multicenter observational study of a representative sample of patients with HCV.
Dr. Kondili and colleagues assessed the medium- and long-term effects of DAA therapy on HCC rates among patients with HCV-induced liver cirrhosis. Patients who had undergone a liver transplant or who had been previously diagnosed with HCC were excluded.
The investigators identified a total of 2,214 DAA-treated patients, of whom 149 (6.7%) developed de novo HCC after a median follow-up of 30 months.
From the total group, 2,064 (93%) patients had an SVR, 119 of whom (5.8%) developed HCC. Of these patients who developed HCC, 80% were diagnosed with stage B or C disease in accordance with the Barcelona Clinic Liver Cancer staging system.
For the remaining 150 patients who did not have an SVR, 30 (20%) developed de novo HCC, a difference that translated into an adjusted hazard ratio (aHR) for HCC of 7.38 (P < .01).
The time from the end of DAA therapy to a diagnosis of HCC was shorter for patients who did not have an SVR. For these patients, the 2-year HCC-free survival rate was 81%, compared with 98% for patients who had an SVR (P < .001).
As reported by Dr. Kondili, among patients who achieved an SVR, the variables significantly associated with HCC risk included older age (aHR, 1.06), platelet counts greater than the reference limit of 150,000 μL (aHR, 2.43), albumin levels >3.5 g/dL (aHR, 2.36), and diabetes (aHR, 1.53; all these variables were significant by confidence intervals).
In all, 26% of these patients died during the follow-up period, and 7.6% underwent liver transplant.
Of the patients still alive at the end of the follow-up period, 38% had active HCC.
Long-term follow-up required
“It’s useful to think of hepatitis C as a viral infection on one hand [and] a liver disease on the other,” commented Raymond T. Chung, MD, director of the Hepatology and Liver Center and vice chief of gastroenterology at Massachusetts General Hospital, Boston.
“In terms of thinking of elimination, we can eradicate the virus in most patients with virtually 100% success with antivirals. This has given us a false sense of comfort that it’s a ‘one and done’ process, and patients can more or less enjoy the rest of their lives free of hepatitis C,” he said.
Dr. Chung, who was not involved in the study, emphasized that despite the elimination of the virus, patients may still have significant liver fibrosis or cirrhosis. It is imperative that these patients be monitored for signs of cancer, he said.
“This is what’s important about staging patients and understanding how severe their liver disease is, because if there is advanced fibrosis, bridging fibrosis, or cirrhosis, these are patients who are going to require long-term oncology care. Their infectious disease is eliminated, but the liver disease remains,” he said.
Dr. Chung also noted that rates of liver cancer, decompensation, and liver failure are higher among patients with untreated HCV than among patients whose HCV has been eradicated or suppressed with drug treatment. In addition, patients with untreated HCV are at greater risk of requiring transplant than are patients with HCV that was treated, and there remains a residual cancer risk for patients who become HCV seronegative.
The study was funded by the Italian Ministry of Health. Dr. Kondili has financial relationships with Gilead Science and AbbVie. Dr. Chung reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although the risk for liver cancer diminishes for patients with hepatitis C virus (HCV) infections for whom the virus is eliminated with direct-acting antiviral (DAA) drugs, these patients are not out of the woods, and those who do not have a sustained viral response (SVR) are at substantially higher risk of developing hepatocellular carcinoma (HCC), results of a large study show.
Among the patients with liver cirrhosis from HCV infections treated at 30 centers in Italy, a large percentage had an SVR after treatment with DAA drugs. Only a small percentage of this group subsequently developed HCC.
In contrast, not having an SVR was associated with a more than sevenfold higher risk for liver cancer, said Loreta A. Kondili, MD, PhD, from the Center for Global Health at the Istituto Superiore di Sanità, Rome, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.
“Failure to achieve SVR after DAA treatment is strongly associated with the probability of HCC development. Older age, [HCV] genotype 3, and low platelet counts and albumin levels are independent factors of HCC development despite viral eradication,” she said.
Cohort study
The study findings come from the PITER Cohort Study, a prospective, multicenter observational study of a representative sample of patients with HCV.
Dr. Kondili and colleagues assessed the medium- and long-term effects of DAA therapy on HCC rates among patients with HCV-induced liver cirrhosis. Patients who had undergone a liver transplant or who had been previously diagnosed with HCC were excluded.
The investigators identified a total of 2,214 DAA-treated patients, of whom 149 (6.7%) developed de novo HCC after a median follow-up of 30 months.
From the total group, 2,064 (93%) patients had an SVR, 119 of whom (5.8%) developed HCC. Of these patients who developed HCC, 80% were diagnosed with stage B or C disease in accordance with the Barcelona Clinic Liver Cancer staging system.
For the remaining 150 patients who did not have an SVR, 30 (20%) developed de novo HCC, a difference that translated into an adjusted hazard ratio (aHR) for HCC of 7.38 (P < .01).
The time from the end of DAA therapy to a diagnosis of HCC was shorter for patients who did not have an SVR. For these patients, the 2-year HCC-free survival rate was 81%, compared with 98% for patients who had an SVR (P < .001).
As reported by Dr. Kondili, among patients who achieved an SVR, the variables significantly associated with HCC risk included older age (aHR, 1.06), platelet counts greater than the reference limit of 150,000 μL (aHR, 2.43), albumin levels >3.5 g/dL (aHR, 2.36), and diabetes (aHR, 1.53; all these variables were significant by confidence intervals).
In all, 26% of these patients died during the follow-up period, and 7.6% underwent liver transplant.
Of the patients still alive at the end of the follow-up period, 38% had active HCC.
Long-term follow-up required
“It’s useful to think of hepatitis C as a viral infection on one hand [and] a liver disease on the other,” commented Raymond T. Chung, MD, director of the Hepatology and Liver Center and vice chief of gastroenterology at Massachusetts General Hospital, Boston.
“In terms of thinking of elimination, we can eradicate the virus in most patients with virtually 100% success with antivirals. This has given us a false sense of comfort that it’s a ‘one and done’ process, and patients can more or less enjoy the rest of their lives free of hepatitis C,” he said.
Dr. Chung, who was not involved in the study, emphasized that despite the elimination of the virus, patients may still have significant liver fibrosis or cirrhosis. It is imperative that these patients be monitored for signs of cancer, he said.
“This is what’s important about staging patients and understanding how severe their liver disease is, because if there is advanced fibrosis, bridging fibrosis, or cirrhosis, these are patients who are going to require long-term oncology care. Their infectious disease is eliminated, but the liver disease remains,” he said.
Dr. Chung also noted that rates of liver cancer, decompensation, and liver failure are higher among patients with untreated HCV than among patients whose HCV has been eradicated or suppressed with drug treatment. In addition, patients with untreated HCV are at greater risk of requiring transplant than are patients with HCV that was treated, and there remains a residual cancer risk for patients who become HCV seronegative.
The study was funded by the Italian Ministry of Health. Dr. Kondili has financial relationships with Gilead Science and AbbVie. Dr. Chung reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Although the risk for liver cancer diminishes for patients with hepatitis C virus (HCV) infections for whom the virus is eliminated with direct-acting antiviral (DAA) drugs, these patients are not out of the woods, and those who do not have a sustained viral response (SVR) are at substantially higher risk of developing hepatocellular carcinoma (HCC), results of a large study show.
Among the patients with liver cirrhosis from HCV infections treated at 30 centers in Italy, a large percentage had an SVR after treatment with DAA drugs. Only a small percentage of this group subsequently developed HCC.
In contrast, not having an SVR was associated with a more than sevenfold higher risk for liver cancer, said Loreta A. Kondili, MD, PhD, from the Center for Global Health at the Istituto Superiore di Sanità, Rome, during a presentation of the findings at The Liver Meeting 2021: American Association for the Study of Liver Diseases (AASLD), held online.
“Failure to achieve SVR after DAA treatment is strongly associated with the probability of HCC development. Older age, [HCV] genotype 3, and low platelet counts and albumin levels are independent factors of HCC development despite viral eradication,” she said.
Cohort study
The study findings come from the PITER Cohort Study, a prospective, multicenter observational study of a representative sample of patients with HCV.
Dr. Kondili and colleagues assessed the medium- and long-term effects of DAA therapy on HCC rates among patients with HCV-induced liver cirrhosis. Patients who had undergone a liver transplant or who had been previously diagnosed with HCC were excluded.
The investigators identified a total of 2,214 DAA-treated patients, of whom 149 (6.7%) developed de novo HCC after a median follow-up of 30 months.
From the total group, 2,064 (93%) patients had an SVR, 119 of whom (5.8%) developed HCC. Of these patients who developed HCC, 80% were diagnosed with stage B or C disease in accordance with the Barcelona Clinic Liver Cancer staging system.
For the remaining 150 patients who did not have an SVR, 30 (20%) developed de novo HCC, a difference that translated into an adjusted hazard ratio (aHR) for HCC of 7.38 (P < .01).
The time from the end of DAA therapy to a diagnosis of HCC was shorter for patients who did not have an SVR. For these patients, the 2-year HCC-free survival rate was 81%, compared with 98% for patients who had an SVR (P < .001).
As reported by Dr. Kondili, among patients who achieved an SVR, the variables significantly associated with HCC risk included older age (aHR, 1.06), platelet counts greater than the reference limit of 150,000 μL (aHR, 2.43), albumin levels >3.5 g/dL (aHR, 2.36), and diabetes (aHR, 1.53; all these variables were significant by confidence intervals).
In all, 26% of these patients died during the follow-up period, and 7.6% underwent liver transplant.
Of the patients still alive at the end of the follow-up period, 38% had active HCC.
Long-term follow-up required
“It’s useful to think of hepatitis C as a viral infection on one hand [and] a liver disease on the other,” commented Raymond T. Chung, MD, director of the Hepatology and Liver Center and vice chief of gastroenterology at Massachusetts General Hospital, Boston.
“In terms of thinking of elimination, we can eradicate the virus in most patients with virtually 100% success with antivirals. This has given us a false sense of comfort that it’s a ‘one and done’ process, and patients can more or less enjoy the rest of their lives free of hepatitis C,” he said.
Dr. Chung, who was not involved in the study, emphasized that despite the elimination of the virus, patients may still have significant liver fibrosis or cirrhosis. It is imperative that these patients be monitored for signs of cancer, he said.
“This is what’s important about staging patients and understanding how severe their liver disease is, because if there is advanced fibrosis, bridging fibrosis, or cirrhosis, these are patients who are going to require long-term oncology care. Their infectious disease is eliminated, but the liver disease remains,” he said.
Dr. Chung also noted that rates of liver cancer, decompensation, and liver failure are higher among patients with untreated HCV than among patients whose HCV has been eradicated or suppressed with drug treatment. In addition, patients with untreated HCV are at greater risk of requiring transplant than are patients with HCV that was treated, and there remains a residual cancer risk for patients who become HCV seronegative.
The study was funded by the Italian Ministry of Health. Dr. Kondili has financial relationships with Gilead Science and AbbVie. Dr. Chung reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Genomic instability varies between breast cancer subtypes
More than 1,000 patients with TNBC, ER+ breast cancer, or ovarian cancer from five cohorts were examined for genomic instability scores (GIS) and the presence of BRCA deficiency, which showed that, while GIS was similar in BRCA-deficient TNBC and ovarian cancer, it was significantly different in ER+ breast cancer.
The analysis, presented at the San Antonio Breast Cancer Symposium, showed that the genomic instability scores threshold, which could be used to dictate a patient’s treatment, should be lower for ER+ breast cancer than for TNBC.
“This indicates that different GIS thresholds are appropriate for breast cancer subtypes, and that the GIS threshold developed for ovarian caner is not appropriate for ER+ breast cancer,” said lead author Kirsten Timms, PhD, from Myriad Genetics.
This, she noted, is “consistent with the fact that ovarian cancer and TNBC are known to have similar molecular signatures.”
The researchers suggest that the “more inclusive” thresholds assessed in the study should be examined in further studies “to determine whether these cutoffs are associated with a benefit from treatment with DNA-targeting agents,” such as poly (ADP-ribose) polymerase (PARP) inhibitors.
Thomas P. Slavin, MD, chief medical officer at Myriad Genetics, said in an interview that there is “not a one size fits all” for GIS thresholds.
“When you look at ER+ breast cancer you see we need a different cutoff because it’s probably not as driven by homologous recombination deficiency [HRD], as least as a whole, compared to the other two,” he said. “There’s a little less genomic instability.”
He continued that their results suggest around half of TNBC patients have a GIS score that indicates the presence of significant HRD, which is “spot on for what we see with ovarian cancer” and “those people should respond pretty well to PARP-inhibitor therapies,” which is currently being investigated in clinical trials.
“But even in the ER+ group, when we look at the thresholds we used in this research, still about a third have what looks like a substantial amount of HRD, so that’s a huge biomarker,” Dr. Slavin said.
He explained that the importance of their score is that, rather than looking for the causes of HRD, they are looking for the consequences.
“We don’t know all the causes of why, all of a sudden, a tumor cell looks like it can’t replicate through homologous combination [but] what this test does is it says: ‘We don’t really care what the cause is ... we can just look at the genomic scarring and the consequences.’ ”
Elena Provenzano, MD, CRUK Therapeutic Discovery Laboratories, Cambridge (England) University Hospitals NHS Foundation Trust, who was not involved in the study, said in an interview it is “interesting work.”
“We have a personalized breast cancer program here in Cambridge and we’re running trials where we use PARP inhibitors and platinum-based therapy, and what we’re using to make these sorts of decisions is COSMIC mutational signatures associated with genetic instability. And I guess we also look at the total mutational burden,” Dr. Provenzano said.
She continued that the GIS is one of several ways of measuring HRD. “So the question is how it compares with the other measures that are being used to assess whether or not patients are suitable for PARP inhibitor and platinum-based therapy.”
Dr. Provenzano underlined that it has been known since the “early 2000s” that breast cancer is a group of different diseases. “Even within those categories there’s quite a lot of tumor types,” so it “makes sense you need to adjust the threshold slightly for it to become relevant to types of breast cancer.”
She added that the “holy grail in oncology is this concept of personalized medicine, so all these tests help us make sure that the right patient is getting the right treatment.
“At the moment TNBC is often getting treated in a similar way, although we know that there are different biological subtypes, so while there’s a significant group that falls into this BRCA-deficient group that are going to respond to PARPs there are other types that don’t.
“So these sorts of tests help us decide which subset are going to help us the most, and for the others ones we potentially need to identify other treatments as being optimal,” Dr. Provenzano said.
Previous studies have shown that HR-deficient tumors may benefit from treatment with DNA-damaging agents, and that tools such as the three-biomarker GIS can be used to identify HR deficiency.
The Food and Drug Administration has already approved a GIS threshold for identifying HR deficiency in ovarian cancer of 42, which was set as the 5th percentile for BRCA-deficient tumors. However, a recent published in Molecular Cancer Research, and a second published on MDPI Open Access Journals, indicated that a lower, first percentile, cutoff of at least 33 was associated with improved outcomes after platinum-based treatment.
As TNBC is known to have a similar molecular profile to ovarian cancer, the researchers investigated whether it has a different GIS threshold to that in ER+ breast cancer, gathering data on patients newly diagnosed with ovarian cancer, TNBC, or ER+ breast cancer from across five cohorts.
They included 127 ovarian cancer patients from Nature, 434 ovarian cancer, 44 TNBC, and 213 ER+ breast cancer patients from The Cancer Genome Atlas, 55 TNBC and 112 ER+ breast cancer patients from Breast Cancer Research, 19 TNBC and 25 ER+ breast cancer patients from TBCRC 008, and 56 ER+ breast cancer patients from OlympiAD.
GIS was defined as a combination of loss of heterozygosity, telomeric-allellic imbalance, and large-scale state transitions, identified through next-generation sequencing, and GIS distributions were compared between cancer types and subtypes.
The team also determined the presence of BRCA deficiency, finding that, among BRCA deficient tumors, the GIS distribution among patients with ER+ breast cancer was significantly different from that seen in both ovarian cancer (P = 9.6 x 10–5) and TNBC (P = 2.1 x 10–4).
The first percentile of a normal distribution of BRCA-deficient ER+ breast cancers indicated a GIS threshold of 24, with 45.1% of all ER+ tumors at or above this threshold found to be GIS positive. This translated into 98.7% of BRCA-deficient tumors and 32.7% that were BRCA intact.
The results also showed, however, that the GIS distribution for TNBC was not significantly different from that seen in ovarian cancer (P = .72), with the threshold of at least 33 Identifying 64.4% of TNBC tumors as GIS positive. This equated to 100% of BRCA-deficient tumors and 41.7% that were BRCA intact.
Dr. Timms and Dr. Slavin are employed by Myriad Genetics, who funded the study.
More than 1,000 patients with TNBC, ER+ breast cancer, or ovarian cancer from five cohorts were examined for genomic instability scores (GIS) and the presence of BRCA deficiency, which showed that, while GIS was similar in BRCA-deficient TNBC and ovarian cancer, it was significantly different in ER+ breast cancer.
The analysis, presented at the San Antonio Breast Cancer Symposium, showed that the genomic instability scores threshold, which could be used to dictate a patient’s treatment, should be lower for ER+ breast cancer than for TNBC.
“This indicates that different GIS thresholds are appropriate for breast cancer subtypes, and that the GIS threshold developed for ovarian caner is not appropriate for ER+ breast cancer,” said lead author Kirsten Timms, PhD, from Myriad Genetics.
This, she noted, is “consistent with the fact that ovarian cancer and TNBC are known to have similar molecular signatures.”
The researchers suggest that the “more inclusive” thresholds assessed in the study should be examined in further studies “to determine whether these cutoffs are associated with a benefit from treatment with DNA-targeting agents,” such as poly (ADP-ribose) polymerase (PARP) inhibitors.
Thomas P. Slavin, MD, chief medical officer at Myriad Genetics, said in an interview that there is “not a one size fits all” for GIS thresholds.
“When you look at ER+ breast cancer you see we need a different cutoff because it’s probably not as driven by homologous recombination deficiency [HRD], as least as a whole, compared to the other two,” he said. “There’s a little less genomic instability.”
He continued that their results suggest around half of TNBC patients have a GIS score that indicates the presence of significant HRD, which is “spot on for what we see with ovarian cancer” and “those people should respond pretty well to PARP-inhibitor therapies,” which is currently being investigated in clinical trials.
“But even in the ER+ group, when we look at the thresholds we used in this research, still about a third have what looks like a substantial amount of HRD, so that’s a huge biomarker,” Dr. Slavin said.
He explained that the importance of their score is that, rather than looking for the causes of HRD, they are looking for the consequences.
“We don’t know all the causes of why, all of a sudden, a tumor cell looks like it can’t replicate through homologous combination [but] what this test does is it says: ‘We don’t really care what the cause is ... we can just look at the genomic scarring and the consequences.’ ”
Elena Provenzano, MD, CRUK Therapeutic Discovery Laboratories, Cambridge (England) University Hospitals NHS Foundation Trust, who was not involved in the study, said in an interview it is “interesting work.”
“We have a personalized breast cancer program here in Cambridge and we’re running trials where we use PARP inhibitors and platinum-based therapy, and what we’re using to make these sorts of decisions is COSMIC mutational signatures associated with genetic instability. And I guess we also look at the total mutational burden,” Dr. Provenzano said.
She continued that the GIS is one of several ways of measuring HRD. “So the question is how it compares with the other measures that are being used to assess whether or not patients are suitable for PARP inhibitor and platinum-based therapy.”
Dr. Provenzano underlined that it has been known since the “early 2000s” that breast cancer is a group of different diseases. “Even within those categories there’s quite a lot of tumor types,” so it “makes sense you need to adjust the threshold slightly for it to become relevant to types of breast cancer.”
She added that the “holy grail in oncology is this concept of personalized medicine, so all these tests help us make sure that the right patient is getting the right treatment.
“At the moment TNBC is often getting treated in a similar way, although we know that there are different biological subtypes, so while there’s a significant group that falls into this BRCA-deficient group that are going to respond to PARPs there are other types that don’t.
“So these sorts of tests help us decide which subset are going to help us the most, and for the others ones we potentially need to identify other treatments as being optimal,” Dr. Provenzano said.
Previous studies have shown that HR-deficient tumors may benefit from treatment with DNA-damaging agents, and that tools such as the three-biomarker GIS can be used to identify HR deficiency.
The Food and Drug Administration has already approved a GIS threshold for identifying HR deficiency in ovarian cancer of 42, which was set as the 5th percentile for BRCA-deficient tumors. However, a recent published in Molecular Cancer Research, and a second published on MDPI Open Access Journals, indicated that a lower, first percentile, cutoff of at least 33 was associated with improved outcomes after platinum-based treatment.
As TNBC is known to have a similar molecular profile to ovarian cancer, the researchers investigated whether it has a different GIS threshold to that in ER+ breast cancer, gathering data on patients newly diagnosed with ovarian cancer, TNBC, or ER+ breast cancer from across five cohorts.
They included 127 ovarian cancer patients from Nature, 434 ovarian cancer, 44 TNBC, and 213 ER+ breast cancer patients from The Cancer Genome Atlas, 55 TNBC and 112 ER+ breast cancer patients from Breast Cancer Research, 19 TNBC and 25 ER+ breast cancer patients from TBCRC 008, and 56 ER+ breast cancer patients from OlympiAD.
GIS was defined as a combination of loss of heterozygosity, telomeric-allellic imbalance, and large-scale state transitions, identified through next-generation sequencing, and GIS distributions were compared between cancer types and subtypes.
The team also determined the presence of BRCA deficiency, finding that, among BRCA deficient tumors, the GIS distribution among patients with ER+ breast cancer was significantly different from that seen in both ovarian cancer (P = 9.6 x 10–5) and TNBC (P = 2.1 x 10–4).
The first percentile of a normal distribution of BRCA-deficient ER+ breast cancers indicated a GIS threshold of 24, with 45.1% of all ER+ tumors at or above this threshold found to be GIS positive. This translated into 98.7% of BRCA-deficient tumors and 32.7% that were BRCA intact.
The results also showed, however, that the GIS distribution for TNBC was not significantly different from that seen in ovarian cancer (P = .72), with the threshold of at least 33 Identifying 64.4% of TNBC tumors as GIS positive. This equated to 100% of BRCA-deficient tumors and 41.7% that were BRCA intact.
Dr. Timms and Dr. Slavin are employed by Myriad Genetics, who funded the study.
More than 1,000 patients with TNBC, ER+ breast cancer, or ovarian cancer from five cohorts were examined for genomic instability scores (GIS) and the presence of BRCA deficiency, which showed that, while GIS was similar in BRCA-deficient TNBC and ovarian cancer, it was significantly different in ER+ breast cancer.
The analysis, presented at the San Antonio Breast Cancer Symposium, showed that the genomic instability scores threshold, which could be used to dictate a patient’s treatment, should be lower for ER+ breast cancer than for TNBC.
“This indicates that different GIS thresholds are appropriate for breast cancer subtypes, and that the GIS threshold developed for ovarian caner is not appropriate for ER+ breast cancer,” said lead author Kirsten Timms, PhD, from Myriad Genetics.
This, she noted, is “consistent with the fact that ovarian cancer and TNBC are known to have similar molecular signatures.”
The researchers suggest that the “more inclusive” thresholds assessed in the study should be examined in further studies “to determine whether these cutoffs are associated with a benefit from treatment with DNA-targeting agents,” such as poly (ADP-ribose) polymerase (PARP) inhibitors.
Thomas P. Slavin, MD, chief medical officer at Myriad Genetics, said in an interview that there is “not a one size fits all” for GIS thresholds.
“When you look at ER+ breast cancer you see we need a different cutoff because it’s probably not as driven by homologous recombination deficiency [HRD], as least as a whole, compared to the other two,” he said. “There’s a little less genomic instability.”
He continued that their results suggest around half of TNBC patients have a GIS score that indicates the presence of significant HRD, which is “spot on for what we see with ovarian cancer” and “those people should respond pretty well to PARP-inhibitor therapies,” which is currently being investigated in clinical trials.
“But even in the ER+ group, when we look at the thresholds we used in this research, still about a third have what looks like a substantial amount of HRD, so that’s a huge biomarker,” Dr. Slavin said.
He explained that the importance of their score is that, rather than looking for the causes of HRD, they are looking for the consequences.
“We don’t know all the causes of why, all of a sudden, a tumor cell looks like it can’t replicate through homologous combination [but] what this test does is it says: ‘We don’t really care what the cause is ... we can just look at the genomic scarring and the consequences.’ ”
Elena Provenzano, MD, CRUK Therapeutic Discovery Laboratories, Cambridge (England) University Hospitals NHS Foundation Trust, who was not involved in the study, said in an interview it is “interesting work.”
“We have a personalized breast cancer program here in Cambridge and we’re running trials where we use PARP inhibitors and platinum-based therapy, and what we’re using to make these sorts of decisions is COSMIC mutational signatures associated with genetic instability. And I guess we also look at the total mutational burden,” Dr. Provenzano said.
She continued that the GIS is one of several ways of measuring HRD. “So the question is how it compares with the other measures that are being used to assess whether or not patients are suitable for PARP inhibitor and platinum-based therapy.”
Dr. Provenzano underlined that it has been known since the “early 2000s” that breast cancer is a group of different diseases. “Even within those categories there’s quite a lot of tumor types,” so it “makes sense you need to adjust the threshold slightly for it to become relevant to types of breast cancer.”
She added that the “holy grail in oncology is this concept of personalized medicine, so all these tests help us make sure that the right patient is getting the right treatment.
“At the moment TNBC is often getting treated in a similar way, although we know that there are different biological subtypes, so while there’s a significant group that falls into this BRCA-deficient group that are going to respond to PARPs there are other types that don’t.
“So these sorts of tests help us decide which subset are going to help us the most, and for the others ones we potentially need to identify other treatments as being optimal,” Dr. Provenzano said.
Previous studies have shown that HR-deficient tumors may benefit from treatment with DNA-damaging agents, and that tools such as the three-biomarker GIS can be used to identify HR deficiency.
The Food and Drug Administration has already approved a GIS threshold for identifying HR deficiency in ovarian cancer of 42, which was set as the 5th percentile for BRCA-deficient tumors. However, a recent published in Molecular Cancer Research, and a second published on MDPI Open Access Journals, indicated that a lower, first percentile, cutoff of at least 33 was associated with improved outcomes after platinum-based treatment.
As TNBC is known to have a similar molecular profile to ovarian cancer, the researchers investigated whether it has a different GIS threshold to that in ER+ breast cancer, gathering data on patients newly diagnosed with ovarian cancer, TNBC, or ER+ breast cancer from across five cohorts.
They included 127 ovarian cancer patients from Nature, 434 ovarian cancer, 44 TNBC, and 213 ER+ breast cancer patients from The Cancer Genome Atlas, 55 TNBC and 112 ER+ breast cancer patients from Breast Cancer Research, 19 TNBC and 25 ER+ breast cancer patients from TBCRC 008, and 56 ER+ breast cancer patients from OlympiAD.
GIS was defined as a combination of loss of heterozygosity, telomeric-allellic imbalance, and large-scale state transitions, identified through next-generation sequencing, and GIS distributions were compared between cancer types and subtypes.
The team also determined the presence of BRCA deficiency, finding that, among BRCA deficient tumors, the GIS distribution among patients with ER+ breast cancer was significantly different from that seen in both ovarian cancer (P = 9.6 x 10–5) and TNBC (P = 2.1 x 10–4).
The first percentile of a normal distribution of BRCA-deficient ER+ breast cancers indicated a GIS threshold of 24, with 45.1% of all ER+ tumors at or above this threshold found to be GIS positive. This translated into 98.7% of BRCA-deficient tumors and 32.7% that were BRCA intact.
The results also showed, however, that the GIS distribution for TNBC was not significantly different from that seen in ovarian cancer (P = .72), with the threshold of at least 33 Identifying 64.4% of TNBC tumors as GIS positive. This equated to 100% of BRCA-deficient tumors and 41.7% that were BRCA intact.
Dr. Timms and Dr. Slavin are employed by Myriad Genetics, who funded the study.
FROM SABCS 2021
Ongoing HER2 breast cancer therapy may cost an additional $68,000 per patient
The current funding policy in British Columbia restricts patients to two lines of HER2-directed therapy for metastatic breast cancer, but accessing continued HER2 suppression has become more complex as novel agents have emerged, Emily Jackson, MD, and colleagues explained (in poster PD8-09) at the San Antonio Breast Cancer Symposium.
Continuing HER2 suppression has improved progression free survival (PFS) and overall survival (OS), but the financial implications of adapting funding policies to “reflect increasing lines of proven HER2 treatment” are unclear, they noted.
Drug funding is provided through the provincial government, but it can take months – and sometimes years – from when a drug is approved by Health Canada and when provincial protocols are approved and funding is made available, Dr. Jackson, co-chief resident (PGY5) at BC Cancer, Vancouver, said in an interview.
During that “lag time,” the province is negotiating drug prices with pharmaceutical companies and determining “which patients are eligible and under which circumstances,” she said.
To assess the potential costs, the investigators analyzed data from the BC Cancer outcomes unit, which collects clinical and outcome information on 85% of all patients diagnosed with breast cancer in the province. Information on therapy use was obtained from the BC Cancer pharmacy database.
Of 230 patients who received any HER2 treatment for metastatic breast cancer dispensed by BC Cancer between 2013 and 2018, 112 (49%) were eligible to continue beyond their second line of therapy.
“Of these, 86 patients accessed continued HER2-directed therapy, while 26 were eligible but unable to access continued HER2Rx,” they reported, noting that “the remaining 51% (n = 118) were not eligible for consideration of further HER2Rx due to either stable disease (n = 61) or deterioration precluding treatment (n = 57).”
At median follow-up of 42.2 months, the median number of lines of therapy in the entire study population was three. The median number of cycles in those who received HER2-directed therapy beyond second-line therapy was 33.
The median overall survival was 37.5 months for those who were eligible but did not continue HER2, compared with 57.9 months for those who did continue, they found.
The overall survival difference was not statistically significant (P = .13), but this was likely due to the small number of patients included in the initial analysis, Dr. Jackson said, noting that the finding is “hypothesis generating,” and should be further assessed.
Notably, most patients who continued HER2 therapy did so through pharmaceutical company compassionate access programs or clinical trials, she said.
The “conservative estimated cost per cycle of HER2Rx” was based on currently available trastuzumab biosimilars, and the potential financial implications were calculated based on the current cost of commonly used third-line therapies.
The findings demonstrate that most patients access continued treatment despite prohibitive funding policies, and suggest that significant increases in cost per patient can be expected if funding policies don’t evolve to meet treatment needs, they concluded, noting that “if these trends in survival continue we would expect an additional cost of $68,000 per patient over current costs.
“As the cost of novel therapies are likely to be higher than currently available biosimilars, there will be significant implications for both private payer and public payer healthcare systems,” they added.
A larger, more comprehensive analysis of the data is planned, said Dr. Jackson, who did not disclose any funding or other conflicts of interest associated with this study.
The current funding policy in British Columbia restricts patients to two lines of HER2-directed therapy for metastatic breast cancer, but accessing continued HER2 suppression has become more complex as novel agents have emerged, Emily Jackson, MD, and colleagues explained (in poster PD8-09) at the San Antonio Breast Cancer Symposium.
Continuing HER2 suppression has improved progression free survival (PFS) and overall survival (OS), but the financial implications of adapting funding policies to “reflect increasing lines of proven HER2 treatment” are unclear, they noted.
Drug funding is provided through the provincial government, but it can take months – and sometimes years – from when a drug is approved by Health Canada and when provincial protocols are approved and funding is made available, Dr. Jackson, co-chief resident (PGY5) at BC Cancer, Vancouver, said in an interview.
During that “lag time,” the province is negotiating drug prices with pharmaceutical companies and determining “which patients are eligible and under which circumstances,” she said.
To assess the potential costs, the investigators analyzed data from the BC Cancer outcomes unit, which collects clinical and outcome information on 85% of all patients diagnosed with breast cancer in the province. Information on therapy use was obtained from the BC Cancer pharmacy database.
Of 230 patients who received any HER2 treatment for metastatic breast cancer dispensed by BC Cancer between 2013 and 2018, 112 (49%) were eligible to continue beyond their second line of therapy.
“Of these, 86 patients accessed continued HER2-directed therapy, while 26 were eligible but unable to access continued HER2Rx,” they reported, noting that “the remaining 51% (n = 118) were not eligible for consideration of further HER2Rx due to either stable disease (n = 61) or deterioration precluding treatment (n = 57).”
At median follow-up of 42.2 months, the median number of lines of therapy in the entire study population was three. The median number of cycles in those who received HER2-directed therapy beyond second-line therapy was 33.
The median overall survival was 37.5 months for those who were eligible but did not continue HER2, compared with 57.9 months for those who did continue, they found.
The overall survival difference was not statistically significant (P = .13), but this was likely due to the small number of patients included in the initial analysis, Dr. Jackson said, noting that the finding is “hypothesis generating,” and should be further assessed.
Notably, most patients who continued HER2 therapy did so through pharmaceutical company compassionate access programs or clinical trials, she said.
The “conservative estimated cost per cycle of HER2Rx” was based on currently available trastuzumab biosimilars, and the potential financial implications were calculated based on the current cost of commonly used third-line therapies.
The findings demonstrate that most patients access continued treatment despite prohibitive funding policies, and suggest that significant increases in cost per patient can be expected if funding policies don’t evolve to meet treatment needs, they concluded, noting that “if these trends in survival continue we would expect an additional cost of $68,000 per patient over current costs.
“As the cost of novel therapies are likely to be higher than currently available biosimilars, there will be significant implications for both private payer and public payer healthcare systems,” they added.
A larger, more comprehensive analysis of the data is planned, said Dr. Jackson, who did not disclose any funding or other conflicts of interest associated with this study.
The current funding policy in British Columbia restricts patients to two lines of HER2-directed therapy for metastatic breast cancer, but accessing continued HER2 suppression has become more complex as novel agents have emerged, Emily Jackson, MD, and colleagues explained (in poster PD8-09) at the San Antonio Breast Cancer Symposium.
Continuing HER2 suppression has improved progression free survival (PFS) and overall survival (OS), but the financial implications of adapting funding policies to “reflect increasing lines of proven HER2 treatment” are unclear, they noted.
Drug funding is provided through the provincial government, but it can take months – and sometimes years – from when a drug is approved by Health Canada and when provincial protocols are approved and funding is made available, Dr. Jackson, co-chief resident (PGY5) at BC Cancer, Vancouver, said in an interview.
During that “lag time,” the province is negotiating drug prices with pharmaceutical companies and determining “which patients are eligible and under which circumstances,” she said.
To assess the potential costs, the investigators analyzed data from the BC Cancer outcomes unit, which collects clinical and outcome information on 85% of all patients diagnosed with breast cancer in the province. Information on therapy use was obtained from the BC Cancer pharmacy database.
Of 230 patients who received any HER2 treatment for metastatic breast cancer dispensed by BC Cancer between 2013 and 2018, 112 (49%) were eligible to continue beyond their second line of therapy.
“Of these, 86 patients accessed continued HER2-directed therapy, while 26 were eligible but unable to access continued HER2Rx,” they reported, noting that “the remaining 51% (n = 118) were not eligible for consideration of further HER2Rx due to either stable disease (n = 61) or deterioration precluding treatment (n = 57).”
At median follow-up of 42.2 months, the median number of lines of therapy in the entire study population was three. The median number of cycles in those who received HER2-directed therapy beyond second-line therapy was 33.
The median overall survival was 37.5 months for those who were eligible but did not continue HER2, compared with 57.9 months for those who did continue, they found.
The overall survival difference was not statistically significant (P = .13), but this was likely due to the small number of patients included in the initial analysis, Dr. Jackson said, noting that the finding is “hypothesis generating,” and should be further assessed.
Notably, most patients who continued HER2 therapy did so through pharmaceutical company compassionate access programs or clinical trials, she said.
The “conservative estimated cost per cycle of HER2Rx” was based on currently available trastuzumab biosimilars, and the potential financial implications were calculated based on the current cost of commonly used third-line therapies.
The findings demonstrate that most patients access continued treatment despite prohibitive funding policies, and suggest that significant increases in cost per patient can be expected if funding policies don’t evolve to meet treatment needs, they concluded, noting that “if these trends in survival continue we would expect an additional cost of $68,000 per patient over current costs.
“As the cost of novel therapies are likely to be higher than currently available biosimilars, there will be significant implications for both private payer and public payer healthcare systems,” they added.
A larger, more comprehensive analysis of the data is planned, said Dr. Jackson, who did not disclose any funding or other conflicts of interest associated with this study.
FROM SABCS 2021