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FDA warning: Lymphoma drug heightens risk of death
The U.S. Food and Drug Administration issued a warning today that the cancer drug duvelisib (Copiktra, Verastem), a PI3 kinase inhibitor, may increase the risk of death and serious side effects.
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib, compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced that it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib following a voluntary request by the drug manufacturer Secura Bio.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by this news organization, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com
The U.S. Food and Drug Administration issued a warning today that the cancer drug duvelisib (Copiktra, Verastem), a PI3 kinase inhibitor, may increase the risk of death and serious side effects.
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib, compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced that it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib following a voluntary request by the drug manufacturer Secura Bio.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by this news organization, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com
The U.S. Food and Drug Administration issued a warning today that the cancer drug duvelisib (Copiktra, Verastem), a PI3 kinase inhibitor, may increase the risk of death and serious side effects.
Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.
However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib, compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.
“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.
More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).
Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.
Of note, in April, the FDA also announced that it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib following a voluntary request by the drug manufacturer Secura Bio.
A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.
This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”
As reported by this news organization, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.
“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.
The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.
A version of this article first appeared on Medscape.com
ctDNA identifies patients with colon cancer who can skip chemo
and also identifies those who are unlikely to benefit, allowing them to skip that treatment.
The results are from the phase 2 DYNAMIC trial.
“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.
The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.
The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.
Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.
The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.
The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.
“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.
“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.
They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
Study details
For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.
The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.
Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).
Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.
ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”
Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
Next steps
The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.
The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.
A version of this article first appeared on Medscape.com.
and also identifies those who are unlikely to benefit, allowing them to skip that treatment.
The results are from the phase 2 DYNAMIC trial.
“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.
The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.
The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.
Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.
The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.
The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.
“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.
“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.
They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
Study details
For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.
The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.
Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).
Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.
ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”
Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
Next steps
The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.
The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.
A version of this article first appeared on Medscape.com.
and also identifies those who are unlikely to benefit, allowing them to skip that treatment.
The results are from the phase 2 DYNAMIC trial.
“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.
The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.
The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.
Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.
The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.
The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.
“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.
“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.
They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
Study details
For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.
The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.
Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).
Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.
ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”
Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
Next steps
The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.
The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.
A version of this article first appeared on Medscape.com.
AT ASCO 2022