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Venetoclax shows promise for r/r hairy cell leukemia
Venetoclax is already approved for adults with chronic lymphocytic leukemia, small lymphocytic leukemia, and as part of a treatment combination in certain patients with acute myeloid leukemia.
The new findings suggest that the drug could also be a chemotherapy-free treatment option for HCL patients after the failure of multiple prior lines of therapy, including vemurafenib plus rituximab, the investigators wrote in a letter to the editor published in the New England Journal of Medicine.
Treatment options for such patients are limited, they noted.
Enrico Tiacci, MD, of the University of Perugia (Italy), and colleagues decided to explore the use of venetoclax in this patient population after reports of in vitro findings showing a possible benefit.
The investigators administered the drug off-label to six patients who had received vemurafenib plus rituximab as their most recent prior therapy; one was resistant and five relapsed after that therapy, they reported. Venetoclax was delivered in 29-day cycles.
After 6 or 12 cycles, two patients experienced complete remission with minimal residual disease (MRD), and one had partial remission, although each had incomplete platelet recovery.
Adding rituximab at a dose of 375 mg per square meter of body-surface area for three to eight cycles improved the depth of response in a patient who had a previous minor response, further reduced MRD in one who had a complete remission to venetoclax, and led to hematologic remission in one who had no response to venetoclax, they noted.
Progression-free survival ranged from 23 to 53-plus months in all five patients who did not have early progression and was similar or better than PFS seen after vemurafenib plus rituximab.
The main toxic effect of venetoclax was worsening of baseline neutropenia, which was sometimes complicated by infections or febrile neutropenia and was managed by dose reductions and granulocyte colony-stimulating factor.
“Thus, venetoclax with or without rituximab may serve as a safe and effective salvage option after failure of vemurafenib plus rituximab treatment, especially in patients who do not require a rapid recovery of blood count,” they concluded.
The study was supported by grants from Fondazione Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health.
A version of this article first appeared on Medscape.com.
Venetoclax is already approved for adults with chronic lymphocytic leukemia, small lymphocytic leukemia, and as part of a treatment combination in certain patients with acute myeloid leukemia.
The new findings suggest that the drug could also be a chemotherapy-free treatment option for HCL patients after the failure of multiple prior lines of therapy, including vemurafenib plus rituximab, the investigators wrote in a letter to the editor published in the New England Journal of Medicine.
Treatment options for such patients are limited, they noted.
Enrico Tiacci, MD, of the University of Perugia (Italy), and colleagues decided to explore the use of venetoclax in this patient population after reports of in vitro findings showing a possible benefit.
The investigators administered the drug off-label to six patients who had received vemurafenib plus rituximab as their most recent prior therapy; one was resistant and five relapsed after that therapy, they reported. Venetoclax was delivered in 29-day cycles.
After 6 or 12 cycles, two patients experienced complete remission with minimal residual disease (MRD), and one had partial remission, although each had incomplete platelet recovery.
Adding rituximab at a dose of 375 mg per square meter of body-surface area for three to eight cycles improved the depth of response in a patient who had a previous minor response, further reduced MRD in one who had a complete remission to venetoclax, and led to hematologic remission in one who had no response to venetoclax, they noted.
Progression-free survival ranged from 23 to 53-plus months in all five patients who did not have early progression and was similar or better than PFS seen after vemurafenib plus rituximab.
The main toxic effect of venetoclax was worsening of baseline neutropenia, which was sometimes complicated by infections or febrile neutropenia and was managed by dose reductions and granulocyte colony-stimulating factor.
“Thus, venetoclax with or without rituximab may serve as a safe and effective salvage option after failure of vemurafenib plus rituximab treatment, especially in patients who do not require a rapid recovery of blood count,” they concluded.
The study was supported by grants from Fondazione Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health.
A version of this article first appeared on Medscape.com.
Venetoclax is already approved for adults with chronic lymphocytic leukemia, small lymphocytic leukemia, and as part of a treatment combination in certain patients with acute myeloid leukemia.
The new findings suggest that the drug could also be a chemotherapy-free treatment option for HCL patients after the failure of multiple prior lines of therapy, including vemurafenib plus rituximab, the investigators wrote in a letter to the editor published in the New England Journal of Medicine.
Treatment options for such patients are limited, they noted.
Enrico Tiacci, MD, of the University of Perugia (Italy), and colleagues decided to explore the use of venetoclax in this patient population after reports of in vitro findings showing a possible benefit.
The investigators administered the drug off-label to six patients who had received vemurafenib plus rituximab as their most recent prior therapy; one was resistant and five relapsed after that therapy, they reported. Venetoclax was delivered in 29-day cycles.
After 6 or 12 cycles, two patients experienced complete remission with minimal residual disease (MRD), and one had partial remission, although each had incomplete platelet recovery.
Adding rituximab at a dose of 375 mg per square meter of body-surface area for three to eight cycles improved the depth of response in a patient who had a previous minor response, further reduced MRD in one who had a complete remission to venetoclax, and led to hematologic remission in one who had no response to venetoclax, they noted.
Progression-free survival ranged from 23 to 53-plus months in all five patients who did not have early progression and was similar or better than PFS seen after vemurafenib plus rituximab.
The main toxic effect of venetoclax was worsening of baseline neutropenia, which was sometimes complicated by infections or febrile neutropenia and was managed by dose reductions and granulocyte colony-stimulating factor.
“Thus, venetoclax with or without rituximab may serve as a safe and effective salvage option after failure of vemurafenib plus rituximab treatment, especially in patients who do not require a rapid recovery of blood count,” they concluded.
The study was supported by grants from Fondazione Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
FDA strengthens mammography regulations: Final rule
A final rule, updating the regulations issued under the Mammography Quality Standards Act of 1992, requires that mammography facilities notify patients about the density of their breasts, strengthens the FDA’s oversight of facilities, and provides guidance to help physicians better categorize and assess mammograms, according to a March 9 press release.
The rule requires implementation of the changes within 18 months.
According to the final rule document, the updates are “intended to improve the delivery of mammography services” in ways that reflect changes in mammography technology, quality standards, and the way results are categorized, reported, and communicated to patients and providers.
For instance, mammography reports must include an assessment of breast density to provide greater detail on the potential limitations of the mammogram results and allow patients and physicians to make more informed decisions, such as the possibility of additional imaging for women with dense breast tissue.
“Today’s action represents the agency’s broader commitment to support innovation to prevent, detect and treat cancer,” said Hilary Marston, MD, MPH, FDA’s chief medical officer, in the agency’s press release. The FDA remains “committed to advancing efforts to improve the health of women and strengthen the fight against breast cancer.”
A version of this article first appeared on Medscape.com.
A final rule, updating the regulations issued under the Mammography Quality Standards Act of 1992, requires that mammography facilities notify patients about the density of their breasts, strengthens the FDA’s oversight of facilities, and provides guidance to help physicians better categorize and assess mammograms, according to a March 9 press release.
The rule requires implementation of the changes within 18 months.
According to the final rule document, the updates are “intended to improve the delivery of mammography services” in ways that reflect changes in mammography technology, quality standards, and the way results are categorized, reported, and communicated to patients and providers.
For instance, mammography reports must include an assessment of breast density to provide greater detail on the potential limitations of the mammogram results and allow patients and physicians to make more informed decisions, such as the possibility of additional imaging for women with dense breast tissue.
“Today’s action represents the agency’s broader commitment to support innovation to prevent, detect and treat cancer,” said Hilary Marston, MD, MPH, FDA’s chief medical officer, in the agency’s press release. The FDA remains “committed to advancing efforts to improve the health of women and strengthen the fight against breast cancer.”
A version of this article first appeared on Medscape.com.
A final rule, updating the regulations issued under the Mammography Quality Standards Act of 1992, requires that mammography facilities notify patients about the density of their breasts, strengthens the FDA’s oversight of facilities, and provides guidance to help physicians better categorize and assess mammograms, according to a March 9 press release.
The rule requires implementation of the changes within 18 months.
According to the final rule document, the updates are “intended to improve the delivery of mammography services” in ways that reflect changes in mammography technology, quality standards, and the way results are categorized, reported, and communicated to patients and providers.
For instance, mammography reports must include an assessment of breast density to provide greater detail on the potential limitations of the mammogram results and allow patients and physicians to make more informed decisions, such as the possibility of additional imaging for women with dense breast tissue.
“Today’s action represents the agency’s broader commitment to support innovation to prevent, detect and treat cancer,” said Hilary Marston, MD, MPH, FDA’s chief medical officer, in the agency’s press release. The FDA remains “committed to advancing efforts to improve the health of women and strengthen the fight against breast cancer.”
A version of this article first appeared on Medscape.com.
Phase 3 results: Ponatinib bests imatinib for Ph+ALL
The agents were evaluated in the randomized, open-label, phase 3 PhALLCON study, the first head-to-head comparison of ponatinib and imatinib in combination with reduced-intensity chemotherapy in the Ph+ALL population.
Overall, patients in the ponatinib arm experienced a significantly higher minimal residual disease (MRD)–negative complete response rate as well as deeper and more durable responses compared with those in the imatinib arm, the investigators reported.
The findings were presented during an American Society of Clinical Oncology virtual plenary session.
In adults with ALL, Ph+ disease is the most frequent genetic subtype, accounting for about one third of cases. The current standard of care for newly diagnosed Ph+ALL, also known as BCR-ABL-1–positive ALL, is BCR-ABL1 TKIs in combination with chemotherapy or steroids. However, when treated with first- or second-generation TKIs, patients eventually progress due to the emergence of treatment resistance.
Before the advent of TKI therapies, Ph+ALL had a very poor prognosis, but the development of imatinib in 2001 was transformative, said Marlise R. Luskin, MD, a senior physician at Dana-Farber Cancer Institute, Boston, in the ASCO plenary session, exploring the state of the science.
Added to “backbone” chemotherapy regimens, imatinib improved complete response rates, increased eligibility for stem cell transplantation, and improved overall survival. Second-generation TKIs, including dasatinib and nilotinib further improved outcomes, said Dr. Luskin, also assistant professor at Harvard Medical School, Boston.
More recently, ponatinib has emerged as a promising treatment given its unique action against the ABLA1 T315I KD mutation present in about 75% of cases that relapse as well as the findings of improved MRD-negative complete response rates and event-free survival in retrospective studies, Dr. Luskin said.
The PhALLCON study was designed to further investigate promising results seen in retrospective studies of ponatinib.
To assess ponatinib versus imatinib, patients were enrolled and randomized two to one to receive either a 30-mg once-daily starting dose of ponatinib or a once-daily 600 mg dose of imatinib plus reduced-intensity chemotherapy. After cycle 20, patients received single agent ponatinib or imatinib until disease progression or unacceptable toxicity.
Of the 245 enrolled, 78 remained on treatment at the August 2022 data cutoff, including 42% of those in the ponatinib arm and 12% in the imatinib arm. The most common reasons for discontinuation included hematopoietic stem cell transplantation (31% for ponatinib and 37% for imatinib), adverse events (12% in both arms), and lack of efficacy (7% and 26%, respectively).
At median follow-up of 20 months among 164 patients in the ponatinib arm and 18 months among 81 patients in the imatinib arm, the MRD-negative complete response rates were 34.4% and 16.7%, respectively, said first author Elias J. Jabbour, MD, a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.
A trend toward improved event-free survival was also observed in the ponatinib arm, but the data were not mature at the time of the analysis, Dr. Jabbour noted.
The two treatments showed comparable safety. Treatment-emergent adverse event rates of any grade and of grade 3 or higher were similar in the two study arms. Arterial occlusive events were infrequent and were also similar between the arms.
“Taken together, for this patient population, the efficacy and safety results demonstrate a favorable risk-benefit assessment for ponatinib, which should be considered a standard of care for frontline therapy in patents with newly diagnosed Ph+ALL,” Dr. Jabbour said.
Although the PhALLCON findings are encouraging, invited discussant Anjali S. Advani, MD, of the Cleveland Clinic, noted some study “pitfalls and caveats,” including the generally younger age and low incidence of cardiovascular risk factors in the study population, which raises questions about the ability to extrapolate the findings to “the larger population, which may be older and have more comorbidities.”
Dr. Advani also said that the ponatinib versus imatinib comparison is a reasonable one, but that most clinicians are now using dasatinib, so “it would have been nice to have this comparison.”
Additionally, “the landscape is now changing with the use of blinatumomab plus TKIs – either dasatinib or ponatinib – in the up-front setting.”
“There is data now from various groups ... showing excellent results, although longer follow-up is needed on all of these,” she said.
One such study is the GIMEMA ALL2820 trial looking at ponatinib plus blinatumomab versus imatinib plus chemotherapy, said Nicolas Boissel, MD, PhD, of Hôpital Saint-Louis in Paris, an invited discussant who addressed the European perspective on the PhALLCON results.
“It is expected that access to ponatinib will be delayed in Europe, compared with the U.S., so meanwhile, clinical trials remain a good option to give access to ponatinib frontline,” he said.
Going forward, Dr. Boissel said it will be important to determine the role of second-generation TKIs in patients who are ineligible to receive ponatinib, the treatment duration needed to reduce long-term risk of relapse, and the potential for eliminating the need for postremission chemotherapy and stem cell transplantation in certain patients.
Dr. Advani added that when evaluating and comparing treatments, it will be important to look at genomic alterations and BCR-ABL mutation status, age and comorbidities, and patterns of disease relapse, including relapse sites and genomics. Longer follow-up results for event-free survival and overall survival are also needed.
“I think, particularly in younger patients with relatively few or no cardiovascular comorbidities, [ponatinib plus reduced-intensity chemotherapy] represents a really exciting option,” Dr. Advani said. “What’s difficult is that the landscape is changing quickly in this field, and so is the standard of care. I think what we struggle with is whether we should be using antibody-based therapies plus TKIs or look at an approach such as this, and further studies are going to be needed to answer that question.”
Dr. Jabbour disclosed ties with Pfizer, Takeda, Amgen, AbbVie, Bristol-Myers Squibb, Incyte, Adaptive Biotechnologies, Astellas Pharma, Genentech, and Ascentage Pharma. Dr. Luskin reported relationships with Pfizer, Novartis, and Abbvie. Dr. Advani disclosed ties with Novartis, Glycomimetics, Kite Pharma, Seattle Genetics, Amgen, Beam Therapeutics, Mkarta, Taiho Oncology, Jazz Pharmaceuticals, Pfizer, and Kura Oncology. Dr. Boissel reported relationships with Amgen, ARIAD/Incyte, Novartis, SERVIER, and Astellas Pharma.
A version of this article originally appeared on Medscape.com.
The agents were evaluated in the randomized, open-label, phase 3 PhALLCON study, the first head-to-head comparison of ponatinib and imatinib in combination with reduced-intensity chemotherapy in the Ph+ALL population.
Overall, patients in the ponatinib arm experienced a significantly higher minimal residual disease (MRD)–negative complete response rate as well as deeper and more durable responses compared with those in the imatinib arm, the investigators reported.
The findings were presented during an American Society of Clinical Oncology virtual plenary session.
In adults with ALL, Ph+ disease is the most frequent genetic subtype, accounting for about one third of cases. The current standard of care for newly diagnosed Ph+ALL, also known as BCR-ABL-1–positive ALL, is BCR-ABL1 TKIs in combination with chemotherapy or steroids. However, when treated with first- or second-generation TKIs, patients eventually progress due to the emergence of treatment resistance.
Before the advent of TKI therapies, Ph+ALL had a very poor prognosis, but the development of imatinib in 2001 was transformative, said Marlise R. Luskin, MD, a senior physician at Dana-Farber Cancer Institute, Boston, in the ASCO plenary session, exploring the state of the science.
Added to “backbone” chemotherapy regimens, imatinib improved complete response rates, increased eligibility for stem cell transplantation, and improved overall survival. Second-generation TKIs, including dasatinib and nilotinib further improved outcomes, said Dr. Luskin, also assistant professor at Harvard Medical School, Boston.
More recently, ponatinib has emerged as a promising treatment given its unique action against the ABLA1 T315I KD mutation present in about 75% of cases that relapse as well as the findings of improved MRD-negative complete response rates and event-free survival in retrospective studies, Dr. Luskin said.
The PhALLCON study was designed to further investigate promising results seen in retrospective studies of ponatinib.
To assess ponatinib versus imatinib, patients were enrolled and randomized two to one to receive either a 30-mg once-daily starting dose of ponatinib or a once-daily 600 mg dose of imatinib plus reduced-intensity chemotherapy. After cycle 20, patients received single agent ponatinib or imatinib until disease progression or unacceptable toxicity.
Of the 245 enrolled, 78 remained on treatment at the August 2022 data cutoff, including 42% of those in the ponatinib arm and 12% in the imatinib arm. The most common reasons for discontinuation included hematopoietic stem cell transplantation (31% for ponatinib and 37% for imatinib), adverse events (12% in both arms), and lack of efficacy (7% and 26%, respectively).
At median follow-up of 20 months among 164 patients in the ponatinib arm and 18 months among 81 patients in the imatinib arm, the MRD-negative complete response rates were 34.4% and 16.7%, respectively, said first author Elias J. Jabbour, MD, a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.
A trend toward improved event-free survival was also observed in the ponatinib arm, but the data were not mature at the time of the analysis, Dr. Jabbour noted.
The two treatments showed comparable safety. Treatment-emergent adverse event rates of any grade and of grade 3 or higher were similar in the two study arms. Arterial occlusive events were infrequent and were also similar between the arms.
“Taken together, for this patient population, the efficacy and safety results demonstrate a favorable risk-benefit assessment for ponatinib, which should be considered a standard of care for frontline therapy in patents with newly diagnosed Ph+ALL,” Dr. Jabbour said.
Although the PhALLCON findings are encouraging, invited discussant Anjali S. Advani, MD, of the Cleveland Clinic, noted some study “pitfalls and caveats,” including the generally younger age and low incidence of cardiovascular risk factors in the study population, which raises questions about the ability to extrapolate the findings to “the larger population, which may be older and have more comorbidities.”
Dr. Advani also said that the ponatinib versus imatinib comparison is a reasonable one, but that most clinicians are now using dasatinib, so “it would have been nice to have this comparison.”
Additionally, “the landscape is now changing with the use of blinatumomab plus TKIs – either dasatinib or ponatinib – in the up-front setting.”
“There is data now from various groups ... showing excellent results, although longer follow-up is needed on all of these,” she said.
One such study is the GIMEMA ALL2820 trial looking at ponatinib plus blinatumomab versus imatinib plus chemotherapy, said Nicolas Boissel, MD, PhD, of Hôpital Saint-Louis in Paris, an invited discussant who addressed the European perspective on the PhALLCON results.
“It is expected that access to ponatinib will be delayed in Europe, compared with the U.S., so meanwhile, clinical trials remain a good option to give access to ponatinib frontline,” he said.
Going forward, Dr. Boissel said it will be important to determine the role of second-generation TKIs in patients who are ineligible to receive ponatinib, the treatment duration needed to reduce long-term risk of relapse, and the potential for eliminating the need for postremission chemotherapy and stem cell transplantation in certain patients.
Dr. Advani added that when evaluating and comparing treatments, it will be important to look at genomic alterations and BCR-ABL mutation status, age and comorbidities, and patterns of disease relapse, including relapse sites and genomics. Longer follow-up results for event-free survival and overall survival are also needed.
“I think, particularly in younger patients with relatively few or no cardiovascular comorbidities, [ponatinib plus reduced-intensity chemotherapy] represents a really exciting option,” Dr. Advani said. “What’s difficult is that the landscape is changing quickly in this field, and so is the standard of care. I think what we struggle with is whether we should be using antibody-based therapies plus TKIs or look at an approach such as this, and further studies are going to be needed to answer that question.”
Dr. Jabbour disclosed ties with Pfizer, Takeda, Amgen, AbbVie, Bristol-Myers Squibb, Incyte, Adaptive Biotechnologies, Astellas Pharma, Genentech, and Ascentage Pharma. Dr. Luskin reported relationships with Pfizer, Novartis, and Abbvie. Dr. Advani disclosed ties with Novartis, Glycomimetics, Kite Pharma, Seattle Genetics, Amgen, Beam Therapeutics, Mkarta, Taiho Oncology, Jazz Pharmaceuticals, Pfizer, and Kura Oncology. Dr. Boissel reported relationships with Amgen, ARIAD/Incyte, Novartis, SERVIER, and Astellas Pharma.
A version of this article originally appeared on Medscape.com.
The agents were evaluated in the randomized, open-label, phase 3 PhALLCON study, the first head-to-head comparison of ponatinib and imatinib in combination with reduced-intensity chemotherapy in the Ph+ALL population.
Overall, patients in the ponatinib arm experienced a significantly higher minimal residual disease (MRD)–negative complete response rate as well as deeper and more durable responses compared with those in the imatinib arm, the investigators reported.
The findings were presented during an American Society of Clinical Oncology virtual plenary session.
In adults with ALL, Ph+ disease is the most frequent genetic subtype, accounting for about one third of cases. The current standard of care for newly diagnosed Ph+ALL, also known as BCR-ABL-1–positive ALL, is BCR-ABL1 TKIs in combination with chemotherapy or steroids. However, when treated with first- or second-generation TKIs, patients eventually progress due to the emergence of treatment resistance.
Before the advent of TKI therapies, Ph+ALL had a very poor prognosis, but the development of imatinib in 2001 was transformative, said Marlise R. Luskin, MD, a senior physician at Dana-Farber Cancer Institute, Boston, in the ASCO plenary session, exploring the state of the science.
Added to “backbone” chemotherapy regimens, imatinib improved complete response rates, increased eligibility for stem cell transplantation, and improved overall survival. Second-generation TKIs, including dasatinib and nilotinib further improved outcomes, said Dr. Luskin, also assistant professor at Harvard Medical School, Boston.
More recently, ponatinib has emerged as a promising treatment given its unique action against the ABLA1 T315I KD mutation present in about 75% of cases that relapse as well as the findings of improved MRD-negative complete response rates and event-free survival in retrospective studies, Dr. Luskin said.
The PhALLCON study was designed to further investigate promising results seen in retrospective studies of ponatinib.
To assess ponatinib versus imatinib, patients were enrolled and randomized two to one to receive either a 30-mg once-daily starting dose of ponatinib or a once-daily 600 mg dose of imatinib plus reduced-intensity chemotherapy. After cycle 20, patients received single agent ponatinib or imatinib until disease progression or unacceptable toxicity.
Of the 245 enrolled, 78 remained on treatment at the August 2022 data cutoff, including 42% of those in the ponatinib arm and 12% in the imatinib arm. The most common reasons for discontinuation included hematopoietic stem cell transplantation (31% for ponatinib and 37% for imatinib), adverse events (12% in both arms), and lack of efficacy (7% and 26%, respectively).
At median follow-up of 20 months among 164 patients in the ponatinib arm and 18 months among 81 patients in the imatinib arm, the MRD-negative complete response rates were 34.4% and 16.7%, respectively, said first author Elias J. Jabbour, MD, a professor of medicine at the University of Texas MD Anderson Cancer Center, Houston.
A trend toward improved event-free survival was also observed in the ponatinib arm, but the data were not mature at the time of the analysis, Dr. Jabbour noted.
The two treatments showed comparable safety. Treatment-emergent adverse event rates of any grade and of grade 3 or higher were similar in the two study arms. Arterial occlusive events were infrequent and were also similar between the arms.
“Taken together, for this patient population, the efficacy and safety results demonstrate a favorable risk-benefit assessment for ponatinib, which should be considered a standard of care for frontline therapy in patents with newly diagnosed Ph+ALL,” Dr. Jabbour said.
Although the PhALLCON findings are encouraging, invited discussant Anjali S. Advani, MD, of the Cleveland Clinic, noted some study “pitfalls and caveats,” including the generally younger age and low incidence of cardiovascular risk factors in the study population, which raises questions about the ability to extrapolate the findings to “the larger population, which may be older and have more comorbidities.”
Dr. Advani also said that the ponatinib versus imatinib comparison is a reasonable one, but that most clinicians are now using dasatinib, so “it would have been nice to have this comparison.”
Additionally, “the landscape is now changing with the use of blinatumomab plus TKIs – either dasatinib or ponatinib – in the up-front setting.”
“There is data now from various groups ... showing excellent results, although longer follow-up is needed on all of these,” she said.
One such study is the GIMEMA ALL2820 trial looking at ponatinib plus blinatumomab versus imatinib plus chemotherapy, said Nicolas Boissel, MD, PhD, of Hôpital Saint-Louis in Paris, an invited discussant who addressed the European perspective on the PhALLCON results.
“It is expected that access to ponatinib will be delayed in Europe, compared with the U.S., so meanwhile, clinical trials remain a good option to give access to ponatinib frontline,” he said.
Going forward, Dr. Boissel said it will be important to determine the role of second-generation TKIs in patients who are ineligible to receive ponatinib, the treatment duration needed to reduce long-term risk of relapse, and the potential for eliminating the need for postremission chemotherapy and stem cell transplantation in certain patients.
Dr. Advani added that when evaluating and comparing treatments, it will be important to look at genomic alterations and BCR-ABL mutation status, age and comorbidities, and patterns of disease relapse, including relapse sites and genomics. Longer follow-up results for event-free survival and overall survival are also needed.
“I think, particularly in younger patients with relatively few or no cardiovascular comorbidities, [ponatinib plus reduced-intensity chemotherapy] represents a really exciting option,” Dr. Advani said. “What’s difficult is that the landscape is changing quickly in this field, and so is the standard of care. I think what we struggle with is whether we should be using antibody-based therapies plus TKIs or look at an approach such as this, and further studies are going to be needed to answer that question.”
Dr. Jabbour disclosed ties with Pfizer, Takeda, Amgen, AbbVie, Bristol-Myers Squibb, Incyte, Adaptive Biotechnologies, Astellas Pharma, Genentech, and Ascentage Pharma. Dr. Luskin reported relationships with Pfizer, Novartis, and Abbvie. Dr. Advani disclosed ties with Novartis, Glycomimetics, Kite Pharma, Seattle Genetics, Amgen, Beam Therapeutics, Mkarta, Taiho Oncology, Jazz Pharmaceuticals, Pfizer, and Kura Oncology. Dr. Boissel reported relationships with Amgen, ARIAD/Incyte, Novartis, SERVIER, and Astellas Pharma.
A version of this article originally appeared on Medscape.com.
Popular book by USC oncologist pulled because of plagiarism
The Los Angeles Times reported earlier this week that it identified at least 95 instances of plagiarism by author David B. Agus, MD, in “The Book of Animal Secrets: Nature’s Lessons for a Long and Happy Life.”
According to the LA Times, Dr. Agus copied passages from numerous sources, including The New York Times, National Geographic, Wikipedia, and smaller niche sites. Some instances involved a sentence or two; others involved multiparagraph, word-for-word copying without attribution.
The book by Dr. Agus – who interviews celebrities for a health-related miniseries on Paramount Plus – had reached the top spot on Amazon’s list of best-selling books about animals a week before its planned March 7 release.
Publisher Simon & Schuster released a statement announcing a recall of the book at Dr. Agus’ expense “until a fully revised and corrected edition can be released.”
Dr. Agus included his own statement apologizing “to the scientists and writers whose work or words were used or not fully attributed,” and said he will “rewrite the passages in question with new language, will provide proper and full attribution, and when ready will announce a new publication date.”
“Writers should always be credited for their work, and I deeply regret these mistakes and the lack of rigor in finalizing the book,” he stated, adding that “[t]his book contains important lessons, messages, and guidance about health that I wanted to convey to the readers. I do not want these mistakes to interfere with that effort.”
A version of this article first appeared on Medscape.com.
The Los Angeles Times reported earlier this week that it identified at least 95 instances of plagiarism by author David B. Agus, MD, in “The Book of Animal Secrets: Nature’s Lessons for a Long and Happy Life.”
According to the LA Times, Dr. Agus copied passages from numerous sources, including The New York Times, National Geographic, Wikipedia, and smaller niche sites. Some instances involved a sentence or two; others involved multiparagraph, word-for-word copying without attribution.
The book by Dr. Agus – who interviews celebrities for a health-related miniseries on Paramount Plus – had reached the top spot on Amazon’s list of best-selling books about animals a week before its planned March 7 release.
Publisher Simon & Schuster released a statement announcing a recall of the book at Dr. Agus’ expense “until a fully revised and corrected edition can be released.”
Dr. Agus included his own statement apologizing “to the scientists and writers whose work or words were used or not fully attributed,” and said he will “rewrite the passages in question with new language, will provide proper and full attribution, and when ready will announce a new publication date.”
“Writers should always be credited for their work, and I deeply regret these mistakes and the lack of rigor in finalizing the book,” he stated, adding that “[t]his book contains important lessons, messages, and guidance about health that I wanted to convey to the readers. I do not want these mistakes to interfere with that effort.”
A version of this article first appeared on Medscape.com.
The Los Angeles Times reported earlier this week that it identified at least 95 instances of plagiarism by author David B. Agus, MD, in “The Book of Animal Secrets: Nature’s Lessons for a Long and Happy Life.”
According to the LA Times, Dr. Agus copied passages from numerous sources, including The New York Times, National Geographic, Wikipedia, and smaller niche sites. Some instances involved a sentence or two; others involved multiparagraph, word-for-word copying without attribution.
The book by Dr. Agus – who interviews celebrities for a health-related miniseries on Paramount Plus – had reached the top spot on Amazon’s list of best-selling books about animals a week before its planned March 7 release.
Publisher Simon & Schuster released a statement announcing a recall of the book at Dr. Agus’ expense “until a fully revised and corrected edition can be released.”
Dr. Agus included his own statement apologizing “to the scientists and writers whose work or words were used or not fully attributed,” and said he will “rewrite the passages in question with new language, will provide proper and full attribution, and when ready will announce a new publication date.”
“Writers should always be credited for their work, and I deeply regret these mistakes and the lack of rigor in finalizing the book,” he stated, adding that “[t]his book contains important lessons, messages, and guidance about health that I wanted to convey to the readers. I do not want these mistakes to interfere with that effort.”
A version of this article first appeared on Medscape.com.
‘Exciting’: Post-SCT, antiviral T-cell therapy shows promise
Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.
In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.
The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.
The findings were published online in Clinical Cancer Research.
Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.
“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”
“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”
Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.
In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.
No patients experienced cytokine release syndrome.
“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.
Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.
The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.
This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.
Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.
In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.
The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.
The findings were published online in Clinical Cancer Research.
Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.
“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”
“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”
Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.
In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.
No patients experienced cytokine release syndrome.
“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.
Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.
The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.
This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.
Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.
In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.
The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.
The findings were published online in Clinical Cancer Research.
Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.
“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”
“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”
Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.
In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.
No patients experienced cytokine release syndrome.
“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.
Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.
The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.
This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.
Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
FROM CLINICAL CANCER RESEARCH
FDA approves pirtobrutinib for r/r mantle cell lymphoma
Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.
“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.
The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.
Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.
The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.
Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.
Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.
“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.
Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”
Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”
The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.
Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.
“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.
The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.
Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.
The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.
Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.
Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.
“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.
Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”
Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”
The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.
Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
Pirtobrutinib is the first and only noncovalent Bruton’s tyrosine kinase inhibitor approved for use in this MCL setting, manufacturer Eli Lilly noted in a press release.
“The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent Bruton’s tyrosine kinase inhibitor,” senior author Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, said in the release.
The approval was based on efficacy demonstrated in the open-label, single-arm, phase 1/2 BRUIN trial – a multicenter study assessing 200 mg once-daily oral pirtobrutinib monotherapy in 120 patients with MCL who had previously received a Bruton’s tyrosine kinase inhibitor, most often ibrutinib (Imbruvica, 67%) acalabrutinib (Calquence, 30%) and zanubrutinib (Brukinsa, 8%). Pirtobrutinib was continued until disease progression or unacceptable toxicity.
Study participants had a median of three prior lines of therapy, and 83% discontinued their last Bruton’s tyrosine kinase inhibitor because of refractory or progressive disease.
The overall response rate in pirtobrutinib-treated patients was 50% with a complete response rate of 13%. Estimated median duration of response was 8.3 months, and the estimated duration of response at 6 months occurred in nearly two-thirds of patients.
Adverse reactions that occurred in at least 15% of patients included fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included decreased neutrophil counts, lymphocyte counts, and platelet counts.
Prescribing information for pirtobrutinib includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies, noted the FDA, which granted priority review, fast track designation, and orphan drug designation for the application submitted by Eli Lilly.
“Jaypirca can reestablish Bruton’s tyrosine kinase inhibition in MCL patients previously treated with a covalent Bruton’s tyrosine kinase inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the Bruton’s tyrosine kinase pathway,” according to Eli Lilly’s release.
Dr. Wang added that the agent “has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients.”
Meghan Gutierrez, CEO at the Lymphoma Research Foundation, also noted that “the approval of Jaypirca brings a new treatment option and, along with that, new hope for people with relapsed or refractory MCL.”
The drug is expected to be available in the United States in the coming weeks, and the confirmatory phase 3 BRUIN trial is currently enrolling patients, Eli Lilly announced. The company also indicated the list price would be $21,000 for a 30-day supply of the 200-mg dose.
Serious adverse events believed to be associated with the use of pirtobrutinib or any medicine or device should be reported to the FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
FDA calls for withdrawal of multiple myeloma drug Pepaxto
(melphalan flufenamide), the company announced in a press release.
The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.
However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).
The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.
The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.
The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.
However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.
That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.
Now, the FDA has requested that the company withdraw its U.S. marketing authorization.
“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.
However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”
Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.
“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.
A version of this article first appeared on Medscape.com.
(melphalan flufenamide), the company announced in a press release.
The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.
However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).
The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.
The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.
The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.
However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.
That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.
Now, the FDA has requested that the company withdraw its U.S. marketing authorization.
“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.
However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”
Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.
“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.
A version of this article first appeared on Medscape.com.
(melphalan flufenamide), the company announced in a press release.
The drug was granted an accelerated approval by the FDA in February 2021, for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.
However, the phase 3 OCEAN study raised concerns about safety, as it showed a higher mortality associated with melphalan flufenamide in the experimental arm, compared with pomalidomide (Pomalyst).
The FDA already flagged this issue in July 2021, issuing a safety alert flagging the increased risk for death observed in the OCEAN trial among patients receiving melphalan flufenamide versus pomalidomide (47.6% vs. 43.4%) and a 5.3-month shorter overall survival.
The issue was also discussed in September 2022 by FDA’s Oncologic Drugs Advisory Committee, which voted 14-to-2 against maintaining the accelerated approval, citing an unfavorable risk/benefit profile.
The company stopped marketing the drug in the United States in October 2021 at the FDA’s request but continued to make it available for patients already undergoing treatment.
However, in March 2022, Oncopeptides rescinded the letter that voluntarily withdrew the agent from market, after further review of overall survival data from the OCEAN trial led the company to reconsider its decision. Notably, marketing efforts were still discontinued while the company worked with the FDA to interpret the data, it stated in the press release.
That review of the data showed that progression-free survival was 42% higher with melphalan flufenamide versus pomalidomide and overall response rates were 32.1% versus 26.5%, respectively.
Now, the FDA has requested that the company withdraw its U.S. marketing authorization.
“We respect FDA’s accelerated approval regulations,” Jakob Lindberg, CEO of Oncopeptides commented in the press release.
However, he also added, “multiple myeloma remains an incurable disease, and the treatment options for patients with triple-class refractory disease will ultimately become exhausted. The OCEAN study demonstrated clinical benefit for multiple myeloma patients, in particular for nontransplanted elderly patients where the unmet medical need remains very high.”
Commercialization of the drug in Europe, under the brand name Pepaxti, is ongoing.
“Pepaxti has a full approval from the European Medicines Agency, EMA, since Aug. 18, 2022, and was approved by the Medicines and Healthcare Products Regulatory Agency, MHRA, in the U.K. on Nov 11, 2022,” the company noted.
A version of this article first appeared on Medscape.com.
Fungi inside cancer cells: ‘A new and emerging hallmark’
The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.
Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.
Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.
The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.
The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”
Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.
The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.
Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.
These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”
Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.
“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”
A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.
Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
A version of this article first appeared on Medscape.com.
The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.
Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.
Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.
The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.
The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”
Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.
The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.
Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.
These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”
Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.
“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”
A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.
Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
A version of this article first appeared on Medscape.com.
The investigators characterized the cancer mycobiome within 17,401 tissue, blood, and plasma samples from four international cohorts, revealing new information about fungi distribution, association with immune cells, and potential prognostic value.
Fungi were detected in all cancer types studied and were often intracellular, reported Lian Narunsky-Haziza, PhD, of Weizmann Institute of Science, Rehovot, Israel, and colleagues.
Additionally, multiple fungal-bacterial-immune ecologies were detected across tumors, and intratumoral fungi stratified clinical outcomes, including immunotherapy response, they noted. Also, cell-free fungal DNA diagnosed healthy and cancer patients in early-stage disease.
The findings, published online in the journal Cell, have potential implications for cancer detection, diagnosis, and treatment, the researchers suggested.
The existence of fungi in most human cancers “is both a surprise and to be expected,” study coauthor Rob Knight, PhD, a professor at the University of California, San Diego, stated in a press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”
Exploration of the associations between cancer and microbes are nothing new, but cancer-associated fungi have rarely been examined, the authors noted.
The findings from this pan-cancer analysis, which suggested “prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers,” complement current “understanding of the interaction between cancer cells and the bacteria that exist in tumors alongside fungi, bacteria that have been shown to affect cancer growth, metastasis, and response to therapy,” they explained.
Of note, the study revealed multiple correlations between the presence of specific fungi in tumors and conditions related to treatment. For example, patients with breast cancer whose tumors contained Malassezia globosa – a fungus found naturally on the skin – had a much lower survival rate than those whose tumors did not contain the fungus. Furthermore, specific fungi were more prevalent in breast tumors from older vs. younger patients, in lung tumors of smokers vs. nonsmokers, and in melanoma tumors that responded to immunotherapy vs. those that did not respond.
These findings suggest that fungal activity is “a new and emerging hallmark of cancer,” stated study coleader Ravid Straussman, PhD, of the Weizmann molecular cell biology department. “These findings should drive us to better explore the potential effects of tumor fungi and to re-examine almost everything we know about cancer through a ‘microbiome lens.’ ”
Unique relationships observed between fungi and bacteria – for example, tumors that contain Aspergillus fungi tended to have specific bacteria in them, whereas tumors that contain Malassezia fungi tended to have other bacteria in them – may have implications for treatment, as they correlated with both tumor immunity and patient survival, according to the authors.
“This study sheds new light on the complex biological environment within tumors, and future research will reveal how fungi affect cancerous growth,” said coauthor Yitzhak Pilpel, PhD, a principal investigator at the Weizmann molecular genetics department. “The fact that fungi can be found not only in cancer cells but also in immune cells implies that, in the future, we’ll probably find that fungi have some effect not only on the cancer cells but also on immune cells and their activity.”
A further finding related to the presence of fungal and bacterial DNA in human blood further suggests that measuring microbial DNA in the blood could lead to early detection of cancer, the authors noted.
Dr. Straussman’s research is supported by the Swiss Society Institute for Cancer Prevention Research, the Fabricant-Morse Families Research Fund for Humanity, the Dr. Chantal d’Adesky Scheinberg Research Fund, and the Dr. Dvora and Haim Teitelbaum Endowment Fund.
A version of this article first appeared on Medscape.com.
FROM CELL
One-third of pancreatic cancer diagnoses missed on scans
say United Kingdom researchers who report a novel analysis.
The study set out to identify the incidence and root causes of missed pancreatic cancer diagnoses on CT and MRI scans, the investigators explained at the United European Gastroenterology Week 2022.
The team studied 600 pancreatic cancer cases, including 46 cases (7.7%) categorized as postimaging pancreatic cancer (PIPC) – cases not detected on imaging performed 3-18 months prior to diagnosis.
They also reviewed 46 CT scans and 4 MRI scans performed in PIPC patients.
The detailed analysis showed that 36% of cases of PIPC were potentially avoidable, reported first author Nosheen Umar, MD, a gastroenterology research fellow at the University of Birmingham (England).
In 10% of PIPC patients, imaging signs associated with pancreatic cancer, such as dilated bile or pancreatic ducts, were not recognized as such and were not investigated further. In 26% of scans, the signs of a mass lesion were not picked up by the radiologist.
The findings are notable as the time window for curative PC surgery is often short, and missing the diagnosis on cross-sectional imaging can result in worse clinical outcomes for patients already dealing with a challenging cancer that has generally poor outcomes, Dr. Umar said in an interview.
In fact, pancreatic cancer has the lowest survival rate of all cancers in Europe, the UEG noted in a press release. Life expectancy at the time of diagnosis is just 4.6 months, and 5-year survival is less than 10%, Dr. Umar said.
Pancreatic cancer causes 95,000 deaths in the European Union each year, the UEG noted, adding that by 2035 the number of cases is predicted to rise by almost 40%.
Details of missed imaging signs
The aim of this study was to establish the most plausible explanations for missed imaging signs of PC, Dr. Umar explained, adding that early diagnosis is vitally important for offering patients the best chance of survival.
Cases analyzed for the study were identified from electronic medical records of adults diagnosed with PC between 2016 and 2021 at two National Health Service providers. An algorithm was developed to categorize PIPC and assess potential causes of the missed diagnoses.
The PIPC cases were categorized by type:
- Type 1 – A focal lesion on previous imaging reported in the same pancreatic segment as PIPC (0% of cases)
- Type 2 – Imaging changes that can be associated with PC reported on previous imaging (20% of cases)
- Type 3 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC, but lesion or imaging changes noted on review after PIPC diagnosis (26% of cases)
- Type 4 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC and no lesion or imaging changes on review after PIPC diagnosis (54% of cases)
“We hope this study will raise awareness of the issue of postimaging pancreatic cancer and common reasons why pancreatic cancer can be initially missed,” Dr. Umar stated in the UEG press release. “This will help to standardize future studies of this issue and guide quality improvement efforts so we can increase the likelihood of an early diagnosis of pancreatic cancer, increase the chances of patient survival and, ultimately, save lives.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
say United Kingdom researchers who report a novel analysis.
The study set out to identify the incidence and root causes of missed pancreatic cancer diagnoses on CT and MRI scans, the investigators explained at the United European Gastroenterology Week 2022.
The team studied 600 pancreatic cancer cases, including 46 cases (7.7%) categorized as postimaging pancreatic cancer (PIPC) – cases not detected on imaging performed 3-18 months prior to diagnosis.
They also reviewed 46 CT scans and 4 MRI scans performed in PIPC patients.
The detailed analysis showed that 36% of cases of PIPC were potentially avoidable, reported first author Nosheen Umar, MD, a gastroenterology research fellow at the University of Birmingham (England).
In 10% of PIPC patients, imaging signs associated with pancreatic cancer, such as dilated bile or pancreatic ducts, were not recognized as such and were not investigated further. In 26% of scans, the signs of a mass lesion were not picked up by the radiologist.
The findings are notable as the time window for curative PC surgery is often short, and missing the diagnosis on cross-sectional imaging can result in worse clinical outcomes for patients already dealing with a challenging cancer that has generally poor outcomes, Dr. Umar said in an interview.
In fact, pancreatic cancer has the lowest survival rate of all cancers in Europe, the UEG noted in a press release. Life expectancy at the time of diagnosis is just 4.6 months, and 5-year survival is less than 10%, Dr. Umar said.
Pancreatic cancer causes 95,000 deaths in the European Union each year, the UEG noted, adding that by 2035 the number of cases is predicted to rise by almost 40%.
Details of missed imaging signs
The aim of this study was to establish the most plausible explanations for missed imaging signs of PC, Dr. Umar explained, adding that early diagnosis is vitally important for offering patients the best chance of survival.
Cases analyzed for the study were identified from electronic medical records of adults diagnosed with PC between 2016 and 2021 at two National Health Service providers. An algorithm was developed to categorize PIPC and assess potential causes of the missed diagnoses.
The PIPC cases were categorized by type:
- Type 1 – A focal lesion on previous imaging reported in the same pancreatic segment as PIPC (0% of cases)
- Type 2 – Imaging changes that can be associated with PC reported on previous imaging (20% of cases)
- Type 3 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC, but lesion or imaging changes noted on review after PIPC diagnosis (26% of cases)
- Type 4 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC and no lesion or imaging changes on review after PIPC diagnosis (54% of cases)
“We hope this study will raise awareness of the issue of postimaging pancreatic cancer and common reasons why pancreatic cancer can be initially missed,” Dr. Umar stated in the UEG press release. “This will help to standardize future studies of this issue and guide quality improvement efforts so we can increase the likelihood of an early diagnosis of pancreatic cancer, increase the chances of patient survival and, ultimately, save lives.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
say United Kingdom researchers who report a novel analysis.
The study set out to identify the incidence and root causes of missed pancreatic cancer diagnoses on CT and MRI scans, the investigators explained at the United European Gastroenterology Week 2022.
The team studied 600 pancreatic cancer cases, including 46 cases (7.7%) categorized as postimaging pancreatic cancer (PIPC) – cases not detected on imaging performed 3-18 months prior to diagnosis.
They also reviewed 46 CT scans and 4 MRI scans performed in PIPC patients.
The detailed analysis showed that 36% of cases of PIPC were potentially avoidable, reported first author Nosheen Umar, MD, a gastroenterology research fellow at the University of Birmingham (England).
In 10% of PIPC patients, imaging signs associated with pancreatic cancer, such as dilated bile or pancreatic ducts, were not recognized as such and were not investigated further. In 26% of scans, the signs of a mass lesion were not picked up by the radiologist.
The findings are notable as the time window for curative PC surgery is often short, and missing the diagnosis on cross-sectional imaging can result in worse clinical outcomes for patients already dealing with a challenging cancer that has generally poor outcomes, Dr. Umar said in an interview.
In fact, pancreatic cancer has the lowest survival rate of all cancers in Europe, the UEG noted in a press release. Life expectancy at the time of diagnosis is just 4.6 months, and 5-year survival is less than 10%, Dr. Umar said.
Pancreatic cancer causes 95,000 deaths in the European Union each year, the UEG noted, adding that by 2035 the number of cases is predicted to rise by almost 40%.
Details of missed imaging signs
The aim of this study was to establish the most plausible explanations for missed imaging signs of PC, Dr. Umar explained, adding that early diagnosis is vitally important for offering patients the best chance of survival.
Cases analyzed for the study were identified from electronic medical records of adults diagnosed with PC between 2016 and 2021 at two National Health Service providers. An algorithm was developed to categorize PIPC and assess potential causes of the missed diagnoses.
The PIPC cases were categorized by type:
- Type 1 – A focal lesion on previous imaging reported in the same pancreatic segment as PIPC (0% of cases)
- Type 2 – Imaging changes that can be associated with PC reported on previous imaging (20% of cases)
- Type 3 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC, but lesion or imaging changes noted on review after PIPC diagnosis (26% of cases)
- Type 4 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC and no lesion or imaging changes on review after PIPC diagnosis (54% of cases)
“We hope this study will raise awareness of the issue of postimaging pancreatic cancer and common reasons why pancreatic cancer can be initially missed,” Dr. Umar stated in the UEG press release. “This will help to standardize future studies of this issue and guide quality improvement efforts so we can increase the likelihood of an early diagnosis of pancreatic cancer, increase the chances of patient survival and, ultimately, save lives.”
The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cost paramount when choosing metastatic breast cancer treatment
While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.
Notably, the authors found that
Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.
“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.
Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.
In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.
The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.
On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.
Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.
But the models did show considerable differences in costs.
The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.
For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.
For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.
Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”
In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.
“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.
The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.
Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.
As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.
The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.
A version of this article first appeared on Medscape.com.
While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.
Notably, the authors found that
Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.
“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.
Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.
In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.
The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.
On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.
Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.
But the models did show considerable differences in costs.
The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.
For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.
For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.
Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”
In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.
“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.
The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.
Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.
As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.
The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.
A version of this article first appeared on Medscape.com.
While efficacy and quality of life outcomes are similar across commonly used treatments for endocrine-refractory or triple-negative metastatic breast cancer, the costs of these agents vary widely, a recent analysis reveals.
Notably, the authors found that
Given “razor thin” differences in outcomes, cost should become a major consideration, the researchers concluded.
“As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs,” first author Stephanie B. Wheeler, PhD, from the University of North Carolina at Chapel Hill, explained in a press release.
Although the drugs Dr. Wheeler and colleagues studied are reimbursed in the metastatic breast cancer setting, “the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice,” Dr. Wheeler said.
In the study, published in the Journal of Clinical Oncology, Dr. Wheeler and colleagues estimated the cost-effectiveness of different therapeutic options from the first- to third-line setting for this patient population.
The researchers used three dynamic microsimulation computer models to predict how hypothetical sets of 10,000 patients with specific types of metastatic breast cancer would respond to various therapy types and sequences. The cohorts were grouped according to prior chemotherapy exposure: cohort 1 had no taxane or anthracycline exposure, cohort 2 had taxane and anthracycline exposure, and cohort 3 had taxane exposure but was anthracycline naive.
On the basis of feedback from oncologists, the investigators focused on different agents in the three cohorts: paclitaxel, capecitabine, or pegylated liposomal doxorubicin for cohort 1; eribulin, capecitabine, or carboplatin for cohort 2; and pegylated liposomal doxorubicin, capecitabine, or eribulin for cohort 3.
Overall, the models showed “nearly indistinguishable differences” in quality of life. In fact, the “razor-thin incremental differences in quality-adjusted survival” across the treatment sequences often amounted to differences of only a few days or weeks, the authors noted, adding that, even in the most extreme of cases, 3 weeks separated the best and worst options for quality-adjusted life-years.
But the models did show considerable differences in costs.
The authors found that, for cohort 1, treatment with paclitaxel followed by capecitabine and then pegylated liposomal doxorubicin corresponded to the highest expected quality-adjusted life-year gain and the lowest costs – $686 per month versus the highest cost option of $1,765.
For cohort 2, treatment with carboplatin followed by capecitabine and then eribulin corresponded to the highest expected quality-adjusted life-year gain and lowest costs.
For cohort 3, treatment sequences beginning with capecitabine or pegylated liposomal doxorubicin followed by eribulin was most cost effective.
Notably, the authors found that eribulin – the most expensive treatment with a high expected adverse event burden – performed particularly poorly in the two cohorts in which it was evaluated, “suggesting it should be used last in a sequence, on the basis of cost-effectiveness alone.”
In other words, “more spending on cancer care does not necessarily confer greater health benefits,” said Dr. Wheeler, also a professor of health policy.
“I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects,” study coauthor Katherine E. Reeder-Hayes, MD, section chief of breast oncology at UNC, said in the press release.
The results demonstrate that therapeutic decisions in the endocrine-refractory or triple-negative metastatic setting “may prioritize costs without affecting clinical outcomes” and highlight the direct impact that a “high-quality, transparent, and accessible economic analysis” can have on patient care, Scott D. Ramsey, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues wrote in an accompanying editorial.
Following the treatment sequences outlined in this study would “reduce patient financial burden and save our health system hundreds of millions of dollars annually,” the editorialists wrote.
As for next steps, Dr. Wheeler and colleagues have developed a financial navigation program to help patients manage their out-of-pocket cancer care costs and are currently scaling up the intervention in nine rural and nonrural oncology practices across North Carolina.
The study was supported by the Center for Disease Control and Prevention through the Prevention Research Centers Program. Dr. Wheeler has received research funding and payment for travel, accommodations, and expenses from Pfizer. Dr. Ramsey has had consulting or advisory roles and has received research funding and/or payment for travel, accommodations, and expenses from Bayer, Genentech, AstraZeneca, Merck, GRAIL, Seattle Genetics, Biovica, and/or Flatiron Health. Because of their editorial roles at the journal, the Journal of Clinical Oncology recused Dr. Wheeler and Dr. Ramsey from having any role in the peer review of their respective manuscripts.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ONCOLOGY