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Sharon Worcester is an award-winning medical journalist for MDedge News. She has been with the company since 1996, first as the Southeast Bureau Chief (1996-2009) when the company was known as International Medical News Group, then as a freelance writer (2010-2015) before returning as a reporter in 2015. She previously worked as a daily newspaper reporter covering health and local government. Sharon currently reports primarily on oncology and hematology. She has a BA from Eckerd College and an MA in Mass Communication/Print Journalism from the University of Florida. Connect with her via LinkedIn and follow her on twitter @SW_MedReporter.
CAR T-cell products shine in real-world setting, reveal new insights
Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.
The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.
who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.
A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.
The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.
Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.
An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.
Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
Predicting outcomes
The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.
A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.
The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.
In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.
“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.
Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”
“These are all real-world data with commercially available products, he noted.
Product selection
Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.
Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.
The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.
Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.
Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.
The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.
who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.
A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.
The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.
Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.
An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.
Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
Predicting outcomes
The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.
A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.
The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.
In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.
“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.
Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”
“These are all real-world data with commercially available products, he noted.
Product selection
Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.
Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.
The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.
Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.
Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.
The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.
who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.
A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.
The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.
Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.
An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.
Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
Predicting outcomes
The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.
A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.
The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.
In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.
“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.
Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”
“These are all real-world data with commercially available products, he noted.
Product selection
Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.
Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.
The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.
Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.
FROM CART21
TITAN: Final results confirm apalutamide benefit in mCSPC
At a median follow-up of 44 months, the median overall survival (OS) was not reached in patients who received apalutamide plus standard androgen deprivation therapy (ADT), but the median OS was 52.2 months in patients who received placebo plus ADT.
“In the final analysis, the risk of death with apalutamide was reduced by 35%, with a hazard ratio of 0.65 and P value of less than .0001. This was similar to the hazard ratio of 0.67 in the primary analysis of TITAN, despite an almost 40% crossover rate from the placebo group to the apalutamide,” said Kim N. Chi, MD, a medical oncologist at BC Cancer Vancouver Prostate Centre.
Dr. Chi reported these results at the 2021 Genitourinary Cancer Symposium (Abstract 11).
Study details
The international, double-blind TITAN trial compared apalutamide (240 mg daily) with placebo, both added to standard ADT, in 1,052 patients with metastatic castration-sensitive prostate cancer, including those with high- and low-volume disease, prior docetaxel use, prior treatment for localized disease, and prior ADT for no more than 6 months.
At the primary analysis, reported in the New England Journal of Medicine in 2019, the dual primary endpoints of radiographic progression-free survival and OS met statistical significance at a median follow up of 22.7 months.
At the final analysis, the median treatment duration was 39.3 months for the apalutamide arm, 20.2 months for the placebo arm, and 15.4 months for patients who crossed over from placebo to apalutamide.
After adjusting for crossover, the effect of apalutamide on OS increased (HR, 0.52), indicating a reduction in the risk of death by 48% versus placebo, Dr. Chi said. He noted that the treatment effect on OS favored apalutamide in both high- and low-volume disease.
“Treatment with apalutamide also significantly prolonged second progression-free survival on next subsequent therapy and delayed development of castration resistance,” Dr. Chi said.
The median second progression-free survival was 44.0 months in the placebo arm and was not reached in the apalutamide arm. The median time to castration resistance was 11.4 months in the placebo arm and was not reached in the apalutamide arm.
Health-related quality of life was also maintained in the apalutamide group throughout the study and did not differ from the placebo group. Safety was consistent with previous reports.
“Importantly, the cumulative incidence of treatment-related falls, fracture, and fatigue was similar between groups, as was the cumulative incidence of treatment-related adverse events and serious adverse events,” Dr. Chi said.
An increased incidence of any-grade rash that was seen in the apalutamide group was expected but plateaued after about 6 months.
“These results confirm the favorable risk-benefit profile of apalutamide,” Dr. Chi concluded.
Implications for practice
The study results raise questions about how to best incorporate the findings into practice, including how to use docetaxel or other androgen receptor inhibitors in treatment strategies for this patient population and if they should be used in high-volume patients, said Elisabeth Heath, MD, session cochair and associate director of translational science at Wayne State University in Detroit.
Dr. Chi said a number of studies over the past 5 years have demonstrated OS benefit when combining ADT with additional therapy.
“Really, this should be considered the standard of care,” he said. “However, real-world studies ... suggest that only a minority of patients are actually receiving this additional therapy.”
Although there are challenges with comparing outcomes across studies to determine which treatments to use, the TITAN data reinforce apalutamide plus ADT as a good option, including in high-volume patients, Dr. Chi said.
Funding for TITAN was provided by Janssen Research & Development. Dr. Chi and Dr. Heath disclosed relationships with Janssen and many other companies. [email protected]
At a median follow-up of 44 months, the median overall survival (OS) was not reached in patients who received apalutamide plus standard androgen deprivation therapy (ADT), but the median OS was 52.2 months in patients who received placebo plus ADT.
“In the final analysis, the risk of death with apalutamide was reduced by 35%, with a hazard ratio of 0.65 and P value of less than .0001. This was similar to the hazard ratio of 0.67 in the primary analysis of TITAN, despite an almost 40% crossover rate from the placebo group to the apalutamide,” said Kim N. Chi, MD, a medical oncologist at BC Cancer Vancouver Prostate Centre.
Dr. Chi reported these results at the 2021 Genitourinary Cancer Symposium (Abstract 11).
Study details
The international, double-blind TITAN trial compared apalutamide (240 mg daily) with placebo, both added to standard ADT, in 1,052 patients with metastatic castration-sensitive prostate cancer, including those with high- and low-volume disease, prior docetaxel use, prior treatment for localized disease, and prior ADT for no more than 6 months.
At the primary analysis, reported in the New England Journal of Medicine in 2019, the dual primary endpoints of radiographic progression-free survival and OS met statistical significance at a median follow up of 22.7 months.
At the final analysis, the median treatment duration was 39.3 months for the apalutamide arm, 20.2 months for the placebo arm, and 15.4 months for patients who crossed over from placebo to apalutamide.
After adjusting for crossover, the effect of apalutamide on OS increased (HR, 0.52), indicating a reduction in the risk of death by 48% versus placebo, Dr. Chi said. He noted that the treatment effect on OS favored apalutamide in both high- and low-volume disease.
“Treatment with apalutamide also significantly prolonged second progression-free survival on next subsequent therapy and delayed development of castration resistance,” Dr. Chi said.
The median second progression-free survival was 44.0 months in the placebo arm and was not reached in the apalutamide arm. The median time to castration resistance was 11.4 months in the placebo arm and was not reached in the apalutamide arm.
Health-related quality of life was also maintained in the apalutamide group throughout the study and did not differ from the placebo group. Safety was consistent with previous reports.
“Importantly, the cumulative incidence of treatment-related falls, fracture, and fatigue was similar between groups, as was the cumulative incidence of treatment-related adverse events and serious adverse events,” Dr. Chi said.
An increased incidence of any-grade rash that was seen in the apalutamide group was expected but plateaued after about 6 months.
“These results confirm the favorable risk-benefit profile of apalutamide,” Dr. Chi concluded.
Implications for practice
The study results raise questions about how to best incorporate the findings into practice, including how to use docetaxel or other androgen receptor inhibitors in treatment strategies for this patient population and if they should be used in high-volume patients, said Elisabeth Heath, MD, session cochair and associate director of translational science at Wayne State University in Detroit.
Dr. Chi said a number of studies over the past 5 years have demonstrated OS benefit when combining ADT with additional therapy.
“Really, this should be considered the standard of care,” he said. “However, real-world studies ... suggest that only a minority of patients are actually receiving this additional therapy.”
Although there are challenges with comparing outcomes across studies to determine which treatments to use, the TITAN data reinforce apalutamide plus ADT as a good option, including in high-volume patients, Dr. Chi said.
Funding for TITAN was provided by Janssen Research & Development. Dr. Chi and Dr. Heath disclosed relationships with Janssen and many other companies. [email protected]
At a median follow-up of 44 months, the median overall survival (OS) was not reached in patients who received apalutamide plus standard androgen deprivation therapy (ADT), but the median OS was 52.2 months in patients who received placebo plus ADT.
“In the final analysis, the risk of death with apalutamide was reduced by 35%, with a hazard ratio of 0.65 and P value of less than .0001. This was similar to the hazard ratio of 0.67 in the primary analysis of TITAN, despite an almost 40% crossover rate from the placebo group to the apalutamide,” said Kim N. Chi, MD, a medical oncologist at BC Cancer Vancouver Prostate Centre.
Dr. Chi reported these results at the 2021 Genitourinary Cancer Symposium (Abstract 11).
Study details
The international, double-blind TITAN trial compared apalutamide (240 mg daily) with placebo, both added to standard ADT, in 1,052 patients with metastatic castration-sensitive prostate cancer, including those with high- and low-volume disease, prior docetaxel use, prior treatment for localized disease, and prior ADT for no more than 6 months.
At the primary analysis, reported in the New England Journal of Medicine in 2019, the dual primary endpoints of radiographic progression-free survival and OS met statistical significance at a median follow up of 22.7 months.
At the final analysis, the median treatment duration was 39.3 months for the apalutamide arm, 20.2 months for the placebo arm, and 15.4 months for patients who crossed over from placebo to apalutamide.
After adjusting for crossover, the effect of apalutamide on OS increased (HR, 0.52), indicating a reduction in the risk of death by 48% versus placebo, Dr. Chi said. He noted that the treatment effect on OS favored apalutamide in both high- and low-volume disease.
“Treatment with apalutamide also significantly prolonged second progression-free survival on next subsequent therapy and delayed development of castration resistance,” Dr. Chi said.
The median second progression-free survival was 44.0 months in the placebo arm and was not reached in the apalutamide arm. The median time to castration resistance was 11.4 months in the placebo arm and was not reached in the apalutamide arm.
Health-related quality of life was also maintained in the apalutamide group throughout the study and did not differ from the placebo group. Safety was consistent with previous reports.
“Importantly, the cumulative incidence of treatment-related falls, fracture, and fatigue was similar between groups, as was the cumulative incidence of treatment-related adverse events and serious adverse events,” Dr. Chi said.
An increased incidence of any-grade rash that was seen in the apalutamide group was expected but plateaued after about 6 months.
“These results confirm the favorable risk-benefit profile of apalutamide,” Dr. Chi concluded.
Implications for practice
The study results raise questions about how to best incorporate the findings into practice, including how to use docetaxel or other androgen receptor inhibitors in treatment strategies for this patient population and if they should be used in high-volume patients, said Elisabeth Heath, MD, session cochair and associate director of translational science at Wayne State University in Detroit.
Dr. Chi said a number of studies over the past 5 years have demonstrated OS benefit when combining ADT with additional therapy.
“Really, this should be considered the standard of care,” he said. “However, real-world studies ... suggest that only a minority of patients are actually receiving this additional therapy.”
Although there are challenges with comparing outcomes across studies to determine which treatments to use, the TITAN data reinforce apalutamide plus ADT as a good option, including in high-volume patients, Dr. Chi said.
Funding for TITAN was provided by Janssen Research & Development. Dr. Chi and Dr. Heath disclosed relationships with Janssen and many other companies. [email protected]
FROM GUCS 2021
Declines in PSA screening may account for rise in metastatic prostate cancers
Between 2008 and 2016, the mean incidence of prostate cancers that were metastatic at diagnosis increased from 6.4 to 9.0 per 100,000 men. During the same period, the mean percentage of men undergoing PSA screening decreased from 61.8% to 50.5%, Vidit Sharma, MD, reported in a poster session at the 2021 Genitourinary Cancers Symposium (Abstract 228).
A random-effects linear regression model demonstrated that longitudinal reductions across states in PSA screening were indeed associated with increased age-adjusted incidence of metastatic prostate cancer, said Dr. Sharma, the lead author of the study and a health services fellow in urologic oncology at the University of California, Los Angeles.
The regression coefficient per 100,000 men was 14.9, confirming that states with greater declines in screening had greater increases in prostate cancers that were metastatic at diagnosis, he added, noting that, “overall, variation in PSA screening explained 27% of the longitudinal variation in metastatic disease at diagnosis.”
Dr. Sharma and colleagues had reviewed North American Association of Central Cancer Registries data from 2002 to 2016 for each state and extracted survey-weighted PSA screening estimates from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System. The researchers noted wide variations in screening across states, but they said across-the-board declines were evident beginning in 2010, marking a “worrisome consequence that needs attention.”
Robert Dreicer, MD, deputy director of the University of Virginia Cancer Center, Charlottesville, agreed, noting in a press statement that the findings suggest reduced PSA screening may come at the cost of more men presenting with metastatic disease.
“Patients should discuss the risks and benefits associated with PSA screening with their doctor to identify the best approach for them,” Dr. Dreicer said.
PSA screening has been shown to reduce prostate cancer metastasis and mortality, but screening has also been linked to overdiagnosis and overtreatment of prostate cancer. As a result, the U.S. Preventive Services Task Force (USPSTF) “found insufficient evidence to recommend PSA screening in 2008 and later recommended against PSA screening in 2012,” Dr. Sharma said.
Several studies subsequently showed a rise in metastatic prostate cancer diagnosis, but the role of PSA screening reductions in those findings was unclear. In 2018, the USPSTF updated its recommendations, stating that men aged 55-69 years should make “an individual decision about whether to be screened after a conversation with their clinician about the potential benefits and harms.”
The task force recommended against PSA screening in men older than 70 years.
The current study “strengthens the epidemiological evidence that reductions in PSA screening may be responsible for at least some of the increase in metastatic prostate cancer diagnoses,” Dr. Sharma said. He added that he and his coauthors support shared decision-making policies to optimize PSA screening approaches to reduce the incidence of metastatic prostate cancer, such as those recommended in the 2018 USPSTF update.
Dr. Sharma disclosed research funding from the Veterans Affairs Health Services Research & Development Fellowship. He and his colleagues had no other disclosures.
Between 2008 and 2016, the mean incidence of prostate cancers that were metastatic at diagnosis increased from 6.4 to 9.0 per 100,000 men. During the same period, the mean percentage of men undergoing PSA screening decreased from 61.8% to 50.5%, Vidit Sharma, MD, reported in a poster session at the 2021 Genitourinary Cancers Symposium (Abstract 228).
A random-effects linear regression model demonstrated that longitudinal reductions across states in PSA screening were indeed associated with increased age-adjusted incidence of metastatic prostate cancer, said Dr. Sharma, the lead author of the study and a health services fellow in urologic oncology at the University of California, Los Angeles.
The regression coefficient per 100,000 men was 14.9, confirming that states with greater declines in screening had greater increases in prostate cancers that were metastatic at diagnosis, he added, noting that, “overall, variation in PSA screening explained 27% of the longitudinal variation in metastatic disease at diagnosis.”
Dr. Sharma and colleagues had reviewed North American Association of Central Cancer Registries data from 2002 to 2016 for each state and extracted survey-weighted PSA screening estimates from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System. The researchers noted wide variations in screening across states, but they said across-the-board declines were evident beginning in 2010, marking a “worrisome consequence that needs attention.”
Robert Dreicer, MD, deputy director of the University of Virginia Cancer Center, Charlottesville, agreed, noting in a press statement that the findings suggest reduced PSA screening may come at the cost of more men presenting with metastatic disease.
“Patients should discuss the risks and benefits associated with PSA screening with their doctor to identify the best approach for them,” Dr. Dreicer said.
PSA screening has been shown to reduce prostate cancer metastasis and mortality, but screening has also been linked to overdiagnosis and overtreatment of prostate cancer. As a result, the U.S. Preventive Services Task Force (USPSTF) “found insufficient evidence to recommend PSA screening in 2008 and later recommended against PSA screening in 2012,” Dr. Sharma said.
Several studies subsequently showed a rise in metastatic prostate cancer diagnosis, but the role of PSA screening reductions in those findings was unclear. In 2018, the USPSTF updated its recommendations, stating that men aged 55-69 years should make “an individual decision about whether to be screened after a conversation with their clinician about the potential benefits and harms.”
The task force recommended against PSA screening in men older than 70 years.
The current study “strengthens the epidemiological evidence that reductions in PSA screening may be responsible for at least some of the increase in metastatic prostate cancer diagnoses,” Dr. Sharma said. He added that he and his coauthors support shared decision-making policies to optimize PSA screening approaches to reduce the incidence of metastatic prostate cancer, such as those recommended in the 2018 USPSTF update.
Dr. Sharma disclosed research funding from the Veterans Affairs Health Services Research & Development Fellowship. He and his colleagues had no other disclosures.
Between 2008 and 2016, the mean incidence of prostate cancers that were metastatic at diagnosis increased from 6.4 to 9.0 per 100,000 men. During the same period, the mean percentage of men undergoing PSA screening decreased from 61.8% to 50.5%, Vidit Sharma, MD, reported in a poster session at the 2021 Genitourinary Cancers Symposium (Abstract 228).
A random-effects linear regression model demonstrated that longitudinal reductions across states in PSA screening were indeed associated with increased age-adjusted incidence of metastatic prostate cancer, said Dr. Sharma, the lead author of the study and a health services fellow in urologic oncology at the University of California, Los Angeles.
The regression coefficient per 100,000 men was 14.9, confirming that states with greater declines in screening had greater increases in prostate cancers that were metastatic at diagnosis, he added, noting that, “overall, variation in PSA screening explained 27% of the longitudinal variation in metastatic disease at diagnosis.”
Dr. Sharma and colleagues had reviewed North American Association of Central Cancer Registries data from 2002 to 2016 for each state and extracted survey-weighted PSA screening estimates from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System. The researchers noted wide variations in screening across states, but they said across-the-board declines were evident beginning in 2010, marking a “worrisome consequence that needs attention.”
Robert Dreicer, MD, deputy director of the University of Virginia Cancer Center, Charlottesville, agreed, noting in a press statement that the findings suggest reduced PSA screening may come at the cost of more men presenting with metastatic disease.
“Patients should discuss the risks and benefits associated with PSA screening with their doctor to identify the best approach for them,” Dr. Dreicer said.
PSA screening has been shown to reduce prostate cancer metastasis and mortality, but screening has also been linked to overdiagnosis and overtreatment of prostate cancer. As a result, the U.S. Preventive Services Task Force (USPSTF) “found insufficient evidence to recommend PSA screening in 2008 and later recommended against PSA screening in 2012,” Dr. Sharma said.
Several studies subsequently showed a rise in metastatic prostate cancer diagnosis, but the role of PSA screening reductions in those findings was unclear. In 2018, the USPSTF updated its recommendations, stating that men aged 55-69 years should make “an individual decision about whether to be screened after a conversation with their clinician about the potential benefits and harms.”
The task force recommended against PSA screening in men older than 70 years.
The current study “strengthens the epidemiological evidence that reductions in PSA screening may be responsible for at least some of the increase in metastatic prostate cancer diagnoses,” Dr. Sharma said. He added that he and his coauthors support shared decision-making policies to optimize PSA screening approaches to reduce the incidence of metastatic prostate cancer, such as those recommended in the 2018 USPSTF update.
Dr. Sharma disclosed research funding from the Veterans Affairs Health Services Research & Development Fellowship. He and his colleagues had no other disclosures.
FROM GUCS 2021
FDA okays new CAR T-cell treatment for large B-cell lymphomas
The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell product for the treatment of adults with certain types of relapsed or refractory large B-cell lymphoma who relapse or fail to respond to at least two systemic treatments.
The new approval comes with a risk evaluation and mitigation strategy (REMS) because of the risk for serious adverse events, including cytokine release syndrome (CRS).
The product, from Juno Therapeutics, a Bristol Myers Squibb company, is the third gene therapy to receive FDA approval for non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma in adults, accounting for about a third of the approximately 77,000 cases diagnosed each year in the United States.
The FDA previously granted Breyanzi orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. The product is the first therapy with an RMAT designation to be licensed by the agency.
The new approval is based on efficacy and safety demonstrated in a pivotal phase 1 trial of more than 250 adults with relapsed or refractory large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%.
“Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities,” the FDA explained. “Both CRS and neurological events can be life-threatening.”
Other side effects, which typically present within 1-2 weeks after treatment, include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system, but some side effects may occur later.
The REMS requires special certification for facilities that dispense the product and “specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi,” the FDA noted.
Breyanzi is not indicated for patients with primary central nervous system lymphoma, the FDA noted.
Facility certification involves training to recognize and manage the risks of CRS and neurologic toxicities.
A postmarketing study to further evaluate the long-term safety will also be required.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell product for the treatment of adults with certain types of relapsed or refractory large B-cell lymphoma who relapse or fail to respond to at least two systemic treatments.
The new approval comes with a risk evaluation and mitigation strategy (REMS) because of the risk for serious adverse events, including cytokine release syndrome (CRS).
The product, from Juno Therapeutics, a Bristol Myers Squibb company, is the third gene therapy to receive FDA approval for non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma in adults, accounting for about a third of the approximately 77,000 cases diagnosed each year in the United States.
The FDA previously granted Breyanzi orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. The product is the first therapy with an RMAT designation to be licensed by the agency.
The new approval is based on efficacy and safety demonstrated in a pivotal phase 1 trial of more than 250 adults with relapsed or refractory large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%.
“Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities,” the FDA explained. “Both CRS and neurological events can be life-threatening.”
Other side effects, which typically present within 1-2 weeks after treatment, include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system, but some side effects may occur later.
The REMS requires special certification for facilities that dispense the product and “specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi,” the FDA noted.
Breyanzi is not indicated for patients with primary central nervous system lymphoma, the FDA noted.
Facility certification involves training to recognize and manage the risks of CRS and neurologic toxicities.
A postmarketing study to further evaluate the long-term safety will also be required.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell product for the treatment of adults with certain types of relapsed or refractory large B-cell lymphoma who relapse or fail to respond to at least two systemic treatments.
The new approval comes with a risk evaluation and mitigation strategy (REMS) because of the risk for serious adverse events, including cytokine release syndrome (CRS).
The product, from Juno Therapeutics, a Bristol Myers Squibb company, is the third gene therapy to receive FDA approval for non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma in adults, accounting for about a third of the approximately 77,000 cases diagnosed each year in the United States.
The FDA previously granted Breyanzi orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. The product is the first therapy with an RMAT designation to be licensed by the agency.
The new approval is based on efficacy and safety demonstrated in a pivotal phase 1 trial of more than 250 adults with relapsed or refractory large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%.
“Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities,” the FDA explained. “Both CRS and neurological events can be life-threatening.”
Other side effects, which typically present within 1-2 weeks after treatment, include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system, but some side effects may occur later.
The REMS requires special certification for facilities that dispense the product and “specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi,” the FDA noted.
Breyanzi is not indicated for patients with primary central nervous system lymphoma, the FDA noted.
Facility certification involves training to recognize and manage the risks of CRS and neurologic toxicities.
A postmarketing study to further evaluate the long-term safety will also be required.
A version of this article first appeared on Medscape.com.
FDA grants MET inhibitor tepotinib accelerated approval for NSCLC
Tepotinib is the first once-daily oral MET inhibitor approved for this patient population, and the approval applies to both treatment-naive and previously treated patients with NSCLC.
The approval was supported by results from the ongoing phase 2 VISION trial. Tepotinib produced an overall response rate of 43% in both treatment-naive patients (n = 69) and previously treated patients (n = 83) in this trial. The median duration of response was 10.8 months and 11.1 months, respectively.
Results of the primary analysis were published in The New England Journal of Medicine last year.
Study subjects received the recommended dose of 450 mg taken as two 225-mg tablets once daily with food until disease progression or unacceptable toxicity. Adverse reactions occurring in at least 20% of patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity also have been reported with tepotinib.
Continued approval of tepotinib “may be contingent upon verification and description of clinical benefit in confirmatory trials,” the FDA stated in an approval announcement.
EMD Serono, the drug’s maker, also announced the approval in a press statement, calling tepotinib “an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”
“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” Paul K. Paik, MD, the VISION primary investigator and clinical director of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York, said in the statement.
“There is a pressing need for targeted treatments that have the potential to generate durable antitumor activity and improve the lives of patients with this challenging disease,” he added.
Andrea Ferris, president and chief executive officer of the nonprofit LUNGevity Foundation, further noted the “powerful progress” made in recent years with respect to understanding genetic mutations in NSCLC.
“The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer,” she said in the statement.
Tepotinib was approved in Japan in March 2020. The drug previously received breakthrough therapy designation and orphan drug designation from the FDA. A marketing authorization application for tepotinib was validated by the European Medicines Agency in November 2020 for a similar indication, EMD Serono reported, adding that applications “have also been submitted in Australia, Switzerland, and Canada under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners.”
Other phase 2 studies of tepotinib are ongoing. The INSIGHT 2 study is designed to test tepotinib in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC with activating EGFR mutations that has progressed following first-line treatment with osimertinib. The PERSPECTIVE study is designed to test tepotinib in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer with acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.
For more details on tepotinib, see the full prescribing information.
Tepotinib is the first once-daily oral MET inhibitor approved for this patient population, and the approval applies to both treatment-naive and previously treated patients with NSCLC.
The approval was supported by results from the ongoing phase 2 VISION trial. Tepotinib produced an overall response rate of 43% in both treatment-naive patients (n = 69) and previously treated patients (n = 83) in this trial. The median duration of response was 10.8 months and 11.1 months, respectively.
Results of the primary analysis were published in The New England Journal of Medicine last year.
Study subjects received the recommended dose of 450 mg taken as two 225-mg tablets once daily with food until disease progression or unacceptable toxicity. Adverse reactions occurring in at least 20% of patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity also have been reported with tepotinib.
Continued approval of tepotinib “may be contingent upon verification and description of clinical benefit in confirmatory trials,” the FDA stated in an approval announcement.
EMD Serono, the drug’s maker, also announced the approval in a press statement, calling tepotinib “an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”
“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” Paul K. Paik, MD, the VISION primary investigator and clinical director of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York, said in the statement.
“There is a pressing need for targeted treatments that have the potential to generate durable antitumor activity and improve the lives of patients with this challenging disease,” he added.
Andrea Ferris, president and chief executive officer of the nonprofit LUNGevity Foundation, further noted the “powerful progress” made in recent years with respect to understanding genetic mutations in NSCLC.
“The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer,” she said in the statement.
Tepotinib was approved in Japan in March 2020. The drug previously received breakthrough therapy designation and orphan drug designation from the FDA. A marketing authorization application for tepotinib was validated by the European Medicines Agency in November 2020 for a similar indication, EMD Serono reported, adding that applications “have also been submitted in Australia, Switzerland, and Canada under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners.”
Other phase 2 studies of tepotinib are ongoing. The INSIGHT 2 study is designed to test tepotinib in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC with activating EGFR mutations that has progressed following first-line treatment with osimertinib. The PERSPECTIVE study is designed to test tepotinib in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer with acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.
For more details on tepotinib, see the full prescribing information.
Tepotinib is the first once-daily oral MET inhibitor approved for this patient population, and the approval applies to both treatment-naive and previously treated patients with NSCLC.
The approval was supported by results from the ongoing phase 2 VISION trial. Tepotinib produced an overall response rate of 43% in both treatment-naive patients (n = 69) and previously treated patients (n = 83) in this trial. The median duration of response was 10.8 months and 11.1 months, respectively.
Results of the primary analysis were published in The New England Journal of Medicine last year.
Study subjects received the recommended dose of 450 mg taken as two 225-mg tablets once daily with food until disease progression or unacceptable toxicity. Adverse reactions occurring in at least 20% of patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity also have been reported with tepotinib.
Continued approval of tepotinib “may be contingent upon verification and description of clinical benefit in confirmatory trials,” the FDA stated in an approval announcement.
EMD Serono, the drug’s maker, also announced the approval in a press statement, calling tepotinib “an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”
“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” Paul K. Paik, MD, the VISION primary investigator and clinical director of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York, said in the statement.
“There is a pressing need for targeted treatments that have the potential to generate durable antitumor activity and improve the lives of patients with this challenging disease,” he added.
Andrea Ferris, president and chief executive officer of the nonprofit LUNGevity Foundation, further noted the “powerful progress” made in recent years with respect to understanding genetic mutations in NSCLC.
“The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer,” she said in the statement.
Tepotinib was approved in Japan in March 2020. The drug previously received breakthrough therapy designation and orphan drug designation from the FDA. A marketing authorization application for tepotinib was validated by the European Medicines Agency in November 2020 for a similar indication, EMD Serono reported, adding that applications “have also been submitted in Australia, Switzerland, and Canada under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners.”
Other phase 2 studies of tepotinib are ongoing. The INSIGHT 2 study is designed to test tepotinib in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC with activating EGFR mutations that has progressed following first-line treatment with osimertinib. The PERSPECTIVE study is designed to test tepotinib in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer with acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.
For more details on tepotinib, see the full prescribing information.
COVID-19 vaccination in cancer patients: NCCN outlines priorities
Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).
In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:
- Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
- Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
- Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
- Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.
Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.
Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
Unique concerns in patients with cancer
The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.
“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.
“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”
Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”
NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.
“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.
“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
Additional vaccine considerations
The NCCN recommendations also address several other issues of importance for cancer patients, including:
- Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
- Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
- Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
- The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.
The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.
Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.
Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).
In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:
- Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
- Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
- Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
- Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.
Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.
Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
Unique concerns in patients with cancer
The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.
“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.
“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”
Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”
NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.
“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.
“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
Additional vaccine considerations
The NCCN recommendations also address several other issues of importance for cancer patients, including:
- Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
- Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
- Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
- The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.
The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.
Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.
Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).
In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:
- Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
- Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
- Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
- Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.
Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.
Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
Unique concerns in patients with cancer
The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.
“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.
“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”
Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”
NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.
“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.
“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
Additional vaccine considerations
The NCCN recommendations also address several other issues of importance for cancer patients, including:
- Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
- Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
- Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
- The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.
The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.
Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.
Most common cancer diagnosis globally: Breast surpasses lung
Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).
Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.
However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.
The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.
These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.
“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.
Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”
To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.
The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).
The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
One in five people will develop cancer
The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.
Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.
Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.
“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.
The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.
A version of this article first appeared on Medscape.com.
Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).
Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.
However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.
The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.
These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.
“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.
Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”
To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.
The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).
The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
One in five people will develop cancer
The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.
Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.
Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.
“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.
The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.
A version of this article first appeared on Medscape.com.
Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).
Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.
However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.
The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.
These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.
“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.
Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”
To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.
The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).
The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
One in five people will develop cancer
The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.
Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.
Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.
“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.
The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.
A version of this article first appeared on Medscape.com.
Breast cancer survival disparities: Need to address obesity
The poorer survival rates in Black women compared with White women with breast cancer could be explained to some extent by the finding of much higher rates of obesity, obesity-related comorbidities, and overall comorbidities in Black women, say researchers reporting a retrospective chart review from their clinic.
Kirsten A. Nyrop, PhD, deputy director for research for the Geriatric Oncology Program at the University of North Carolina, Chapel Hill, and colleagues analyzed medical charts for 144 Black women and 404 White women with early breast cancer.
Obesity rates were nearly double among Black women, at 62% vs 32%.
In addition, significantly more Black women had two or more total comorbidities (62% vs 47%), two or more obesity-related comorbidities (33% vs 10%), hypertension (60% vs 32%), type 2 diabetes (23% vs 6%), and hypercholesterolemia or hyperlipidemia (28% vs 18%).
These racial disparities persisted after adjustment for age and body mass index, both independent predictors of chronic diseases.
The difference in obesity and comorbidity did not translate to differences in treatment decisions such as surgery type, chemotherapy regimen, radiation, or endocrine treatment, the researchers note.
The findings were published online December 7 in the journal Cancer.
They underscore the likely role of obesity and related complications in the racial disparities seen in breast cancer survival outcomes, the authors conclude.
Experts writing in an accompanying editorial agree, while emphasizing the well documented differences in survival.
Compared with White women with breast cancer, Black women with breast cancer have a 42% higher mortality rate and a greater likelihood of dying from breast cancer regardless of their age at diagnosis, note Caitlin E. Taylor, MD, and Jane Lowe Meisel, MD, of Emory University, Atlanta, Georgia.
“Although it is clear that the causes of such disparities are complex and multifactorial, questions remain regarding to what extent patient comorbidities, and specifically obesity, may be playing a role,” they write.
The obesity- and comorbidity-related disparities identified by Nyrop et al “undoubtedly contribute to the overall disparities noted in breast cancer outcomes among Black women,” they add.
Takeaway messages
Nyrop and colleagues say their findings have two important takeaway messages:
1) It is important to manage comorbidities in women with newly diagnosed early breast cancer to reduce the risk of mortality from competing causes, and
2) Excess weight at diagnosis and weight gain after primary treatment increase the risk of obesity-related disease that can affect survival, and patients should be educated about the association.
Such conversations should be “patient-centered and culturally appropriate,” they note.
In their editorial, Taylor and Meisel agree with the authors’ conclusions. “Given the higher prevalence of obesity and related comorbidities among Black patients, addressing these issues must become an integral part of early breast cancer management to prolong overall survival and continue improving outcomes for these women.”
In fact, addressing comorbidities early in breast cancer management is important for patients of all racial and ethnic backgrounds, the editorialists add, concluding that the role of obesity as “a critical player underlying breast cancer mortality” is increasingly clear, and that its management is crucial for improved outcomes and quality of life.
This study was supported by the Breast Cancer Research Foundation, the National Cancer Institute’s Breast Cancer Specialized Program of Research Excellence, and the University of North Carolina Lineberger Comprehensive Cancer Center/University Cancer Research Fund. The study authors have disclosed no relevant financial relationships. Meisel has received research support from Pfizer, Eli Lilly, and Seattle Genetics and has served as a paid advisor for Pfizer, PUMA, Novartis, and Clovis Oncology. Taylor has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The poorer survival rates in Black women compared with White women with breast cancer could be explained to some extent by the finding of much higher rates of obesity, obesity-related comorbidities, and overall comorbidities in Black women, say researchers reporting a retrospective chart review from their clinic.
Kirsten A. Nyrop, PhD, deputy director for research for the Geriatric Oncology Program at the University of North Carolina, Chapel Hill, and colleagues analyzed medical charts for 144 Black women and 404 White women with early breast cancer.
Obesity rates were nearly double among Black women, at 62% vs 32%.
In addition, significantly more Black women had two or more total comorbidities (62% vs 47%), two or more obesity-related comorbidities (33% vs 10%), hypertension (60% vs 32%), type 2 diabetes (23% vs 6%), and hypercholesterolemia or hyperlipidemia (28% vs 18%).
These racial disparities persisted after adjustment for age and body mass index, both independent predictors of chronic diseases.
The difference in obesity and comorbidity did not translate to differences in treatment decisions such as surgery type, chemotherapy regimen, radiation, or endocrine treatment, the researchers note.
The findings were published online December 7 in the journal Cancer.
They underscore the likely role of obesity and related complications in the racial disparities seen in breast cancer survival outcomes, the authors conclude.
Experts writing in an accompanying editorial agree, while emphasizing the well documented differences in survival.
Compared with White women with breast cancer, Black women with breast cancer have a 42% higher mortality rate and a greater likelihood of dying from breast cancer regardless of their age at diagnosis, note Caitlin E. Taylor, MD, and Jane Lowe Meisel, MD, of Emory University, Atlanta, Georgia.
“Although it is clear that the causes of such disparities are complex and multifactorial, questions remain regarding to what extent patient comorbidities, and specifically obesity, may be playing a role,” they write.
The obesity- and comorbidity-related disparities identified by Nyrop et al “undoubtedly contribute to the overall disparities noted in breast cancer outcomes among Black women,” they add.
Takeaway messages
Nyrop and colleagues say their findings have two important takeaway messages:
1) It is important to manage comorbidities in women with newly diagnosed early breast cancer to reduce the risk of mortality from competing causes, and
2) Excess weight at diagnosis and weight gain after primary treatment increase the risk of obesity-related disease that can affect survival, and patients should be educated about the association.
Such conversations should be “patient-centered and culturally appropriate,” they note.
In their editorial, Taylor and Meisel agree with the authors’ conclusions. “Given the higher prevalence of obesity and related comorbidities among Black patients, addressing these issues must become an integral part of early breast cancer management to prolong overall survival and continue improving outcomes for these women.”
In fact, addressing comorbidities early in breast cancer management is important for patients of all racial and ethnic backgrounds, the editorialists add, concluding that the role of obesity as “a critical player underlying breast cancer mortality” is increasingly clear, and that its management is crucial for improved outcomes and quality of life.
This study was supported by the Breast Cancer Research Foundation, the National Cancer Institute’s Breast Cancer Specialized Program of Research Excellence, and the University of North Carolina Lineberger Comprehensive Cancer Center/University Cancer Research Fund. The study authors have disclosed no relevant financial relationships. Meisel has received research support from Pfizer, Eli Lilly, and Seattle Genetics and has served as a paid advisor for Pfizer, PUMA, Novartis, and Clovis Oncology. Taylor has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
The poorer survival rates in Black women compared with White women with breast cancer could be explained to some extent by the finding of much higher rates of obesity, obesity-related comorbidities, and overall comorbidities in Black women, say researchers reporting a retrospective chart review from their clinic.
Kirsten A. Nyrop, PhD, deputy director for research for the Geriatric Oncology Program at the University of North Carolina, Chapel Hill, and colleagues analyzed medical charts for 144 Black women and 404 White women with early breast cancer.
Obesity rates were nearly double among Black women, at 62% vs 32%.
In addition, significantly more Black women had two or more total comorbidities (62% vs 47%), two or more obesity-related comorbidities (33% vs 10%), hypertension (60% vs 32%), type 2 diabetes (23% vs 6%), and hypercholesterolemia or hyperlipidemia (28% vs 18%).
These racial disparities persisted after adjustment for age and body mass index, both independent predictors of chronic diseases.
The difference in obesity and comorbidity did not translate to differences in treatment decisions such as surgery type, chemotherapy regimen, radiation, or endocrine treatment, the researchers note.
The findings were published online December 7 in the journal Cancer.
They underscore the likely role of obesity and related complications in the racial disparities seen in breast cancer survival outcomes, the authors conclude.
Experts writing in an accompanying editorial agree, while emphasizing the well documented differences in survival.
Compared with White women with breast cancer, Black women with breast cancer have a 42% higher mortality rate and a greater likelihood of dying from breast cancer regardless of their age at diagnosis, note Caitlin E. Taylor, MD, and Jane Lowe Meisel, MD, of Emory University, Atlanta, Georgia.
“Although it is clear that the causes of such disparities are complex and multifactorial, questions remain regarding to what extent patient comorbidities, and specifically obesity, may be playing a role,” they write.
The obesity- and comorbidity-related disparities identified by Nyrop et al “undoubtedly contribute to the overall disparities noted in breast cancer outcomes among Black women,” they add.
Takeaway messages
Nyrop and colleagues say their findings have two important takeaway messages:
1) It is important to manage comorbidities in women with newly diagnosed early breast cancer to reduce the risk of mortality from competing causes, and
2) Excess weight at diagnosis and weight gain after primary treatment increase the risk of obesity-related disease that can affect survival, and patients should be educated about the association.
Such conversations should be “patient-centered and culturally appropriate,” they note.
In their editorial, Taylor and Meisel agree with the authors’ conclusions. “Given the higher prevalence of obesity and related comorbidities among Black patients, addressing these issues must become an integral part of early breast cancer management to prolong overall survival and continue improving outcomes for these women.”
In fact, addressing comorbidities early in breast cancer management is important for patients of all racial and ethnic backgrounds, the editorialists add, concluding that the role of obesity as “a critical player underlying breast cancer mortality” is increasingly clear, and that its management is crucial for improved outcomes and quality of life.
This study was supported by the Breast Cancer Research Foundation, the National Cancer Institute’s Breast Cancer Specialized Program of Research Excellence, and the University of North Carolina Lineberger Comprehensive Cancer Center/University Cancer Research Fund. The study authors have disclosed no relevant financial relationships. Meisel has received research support from Pfizer, Eli Lilly, and Seattle Genetics and has served as a paid advisor for Pfizer, PUMA, Novartis, and Clovis Oncology. Taylor has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
VTE prophylaxis is feasible, effective in some high-risk cancer patients
Primary thromboprophylaxis is feasible and worth considering for high-risk ambulatory patients with cancer who are initiating systemic chemotherapy, according to Marc Carrier, MD.
Risk scores can identify patients at high risk for venous thromboembolism (VTE), and treatments that are effective and associated with low bleeding risk are available, Dr. Carrier explained at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
However, caution is advised in patients with certain types of cancer, including some gastrointestinal and genitourinary cancers, because of the possibility of increased major and clinically relevant nonmajor bleeding risk, he said.
VTE and cancer
VTE is relatively rare in the general population, occurring in about 1 or 2 per 1,000 people annually. The risk increases 4.1-fold in patients with cancer, and 6.5-fold in patients with cancer receiving chemotherapy.
“So just putting these numbers together, we’re no longer talking about 1 in 1,000, but 1 in 200, so [this is] something that is very common among cancer patients,” said Dr. Carrier, a professor at the University of Ottawa and chief of the division of hematology at The Ottawa Hospital.
The mortality rate associated with cancer-associated thrombosis is about 9%, comparable to that associated with infection in the cancer outpatient setting, which underscores the importance of educating patients about the signs and symptoms of VTE so they can seek medical treatment quickly if necessary, he added.
It may also be useful to discuss prophylaxis or other ways to prevent venous thromboembolic complications with certain patients, he said, noting that in an observational cohort study of nearly 600 patients at the University of Ottawa, 25% of those initiating chemotherapy were identified as intermediate or high risk using the validated Khorana risk score, and thus would likely benefit from thromboprophylaxis.
Risk assessment
The Khorana risk score assesses VTE risk based on cancer site, blood counts, and body mass index. It is simple to use and has been validated in more than 20,000 people in multiple countries, Dr. Carrier said.
In a well-known validation study, Ay et al. showed a VTE complication rate of 10% in patients with a Khorana risk score of 2 or higher who were followed up to 6 months.
“This is huge,” Dr. Carrier stressed. “This is much higher than what we tolerate for all sorts of different populations for which we would recommend anticoagulation or thromboprophylaxis.”
The question is whether the risk score can be helpful in a real-world clinic setting, he said, adding: “I’d like to think the answer to that is yes.”
In the University of Ottawa cohort study, 11% of high-risk patients experienced a VTE complication, compared with 4% of those with lower risk, suggesting that the validation data for the Khorana risk score is not only accurate, it is “actually applicable in real-world practice, and you can use it in your own center,” he said.
Further, recent studies have demonstrated that treatment based on Khorana risk score assessment reduces VTE complications.
Prophylaxis options
Low-molecular-weight heparin (LMWH) has been shown in several studies to be associated with a significant relative VTE risk reduction in patients with cancer initiating chemotherapy – with only a slight, nonsignificant increase in the risk of major bleeding.
However, the absolute benefit was small, and LMWH is “parenteral, relatively costly, and, based on that, although we showed relatively good risk-benefit ratio, it never really got translated to clinical practice,” Dr. Carrier said.
In fact, a 2015 American Society of Clinical Oncology guidelines update recommended against routine thromboprophylaxis in this setting, but stated that it could be considered in select high-risk patients identified using a validated risk-assessment tool.
The guidelines noted that “individual risk factors such as biomarkers and cancer site don’t reliably identify high-risk patients.”
More recent data provide additional support for risk assessment and treatment based on Khorana risk score of 2 or higher.
The AVERT trial, for which Dr. Carrier was the first author, showed that the direct-acting oral anticoagulant (DOAC) apixaban reduced VTE incidence, compared with placebo, in patients with Khorana score of 2 or higher (4.2% vs. 10.2%; hazard ratio, 0.41 overall, and 1.0 vs. 7.3; HR, 0.14 on treatment), and the CASSINI trial showed that another DOAC, rivaroxaban, reduced VTE incidence, compared with placebo, in those with Khorana score of 2 or higher (5.9 vs. 6.7; HR, 0.6 overall, and 2.6 vs. 6.4; HR, 0.40 on treatment). The differences in the on-treatment populations were statistically significant.
The two trials, which included a variety of tumor types, showed similar rates of major bleeding, with an absolute difference of about 1% between treatment and placebo, which was not statistically significant in the on-treatment analyses (HR, 1.89 in AVERT and HR, 1.96 in CASSINI).
A systematic review of these trials showed an overall significant decrease in VTE complication risk with treatment in high-risk patients, and a nonstatistically significant major bleeding risk increase.
Based on these findings, ASCO guidelines were updated in 2020 to state that “routine thromboprophylaxis should not be offered to all patients with cancer. ... However, high-risk outpatients with cancer may be offered thromboprophylaxis with apixaban, rivaroxaban or LMWH, providing there are no significant risk factors for bleeding or drug-drug interactions, and after having a full discussion with patients ... to make sure they understand the risk-benefit ratio and the rationale for that particular recommendation,” he said.
Real-world implementation
Implementing this approach in the clinic setting requires a practical model, such as the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) program, a prospective quality improvement research initiative developed in collaboration with the Jeffords Institute for Quality at the University of Vermont Medical Center and described in a recent report, Dr. Carrier said.
The “Vermont model” is “really a comprehensive model that includes identifying patients with the electronic medical records, gathering the formal education and insight from other health care providers like pharmacists and nurses in order to really come up with personalized care for your patients,” he explained.
In 918 outpatients with cancer who were included in the program, VTE awareness increased from less than 5% before VTEPACC to nearly 82% during the implementation phase and 94.7% after 2 years, with nearly 94% of high-risk patients receiving VTE prophylaxis at that time.
“So we can certainly do that in our own center.” he said. “It’s a matter of coming up with the model and making sure that the patients are seen at the right time.”
Given the high frequency of VTE in patients with cancer initiating chemotherapy, the usefulness of risk scores such as the Khorana risk score for identifying those at high risk, and the availability of safe and effective interventions for reducing risk, “we should probably use the data and incorporate them into clinical practice by implementation of programs for primary prevention,” he said.
A word of caution
Caution is warranted, however, when it comes to using DOACs in patients with higher-risk or potentially higher-risk tumor types, he added.
“It’s an important question we are facing as clinicians on a daily basis,” he said, responding to an attendee’s query, as shared by session moderator James Douketis, MD, professor of medicine at McMaster University, Hamilton, Ont., regarding possible bleeding risks in certain genitourinary cancers.
A recent meta-analysis published in Nature, for example, noted that, in the SELECT-D trial, rivaroxaban was associated with significantly higher incidence of clinically relevant nonmajor bleeding, most often in bladder and colorectal cancers, and most often at genitourinary and gastrointestinal sites.
Both Dr. Carrier and fellow panelist Michael Streiff, MD, professor of medicine at Johns Hopkins University and medical director at the Johns Hopkins Hospital Special Coagulation Laboratory, Baltimore, said they approach DOAC use cautiously, but don’t rule it out entirely, in patients with unresected genitourinary tumors that could pose a risk of bleeding.
“It’s worth mentioning and being cautious. In my own personal practice, I’m very careful with unresected urothelial-type tumors or, for example, bladder cancer, for the same reason as [with] unresected luminal GI tumors,” Dr. Carrier said, adding that he’s also mindful that patients with nephropathy were excluded from U.S. DOAC trials because of bleeding risk.
He said he sometimes tries a LMWH challenge first in higher-risk patients, and then might try a DOAC if no bleeding occurs.
“But it certainly is controversial,” he noted.
Dr. Streiff added that he also worries less with genitourinary cancers than with upper GI lesions because “the signals weren’t as big as in GI” cancers, but he noted that “the drugs are going out through the kidneys ... so I’m cautious in those populations.”
“So caution, but not complete exclusion, is the operative management,” Dr. Douketis said, summarizing the panelists’ consensus.
Dr. Carrier reported clinical trial or advisory board participation for Bayer, Pfizer, Servier, Leo Pharma, and/or BMS.
Primary thromboprophylaxis is feasible and worth considering for high-risk ambulatory patients with cancer who are initiating systemic chemotherapy, according to Marc Carrier, MD.
Risk scores can identify patients at high risk for venous thromboembolism (VTE), and treatments that are effective and associated with low bleeding risk are available, Dr. Carrier explained at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
However, caution is advised in patients with certain types of cancer, including some gastrointestinal and genitourinary cancers, because of the possibility of increased major and clinically relevant nonmajor bleeding risk, he said.
VTE and cancer
VTE is relatively rare in the general population, occurring in about 1 or 2 per 1,000 people annually. The risk increases 4.1-fold in patients with cancer, and 6.5-fold in patients with cancer receiving chemotherapy.
“So just putting these numbers together, we’re no longer talking about 1 in 1,000, but 1 in 200, so [this is] something that is very common among cancer patients,” said Dr. Carrier, a professor at the University of Ottawa and chief of the division of hematology at The Ottawa Hospital.
The mortality rate associated with cancer-associated thrombosis is about 9%, comparable to that associated with infection in the cancer outpatient setting, which underscores the importance of educating patients about the signs and symptoms of VTE so they can seek medical treatment quickly if necessary, he added.
It may also be useful to discuss prophylaxis or other ways to prevent venous thromboembolic complications with certain patients, he said, noting that in an observational cohort study of nearly 600 patients at the University of Ottawa, 25% of those initiating chemotherapy were identified as intermediate or high risk using the validated Khorana risk score, and thus would likely benefit from thromboprophylaxis.
Risk assessment
The Khorana risk score assesses VTE risk based on cancer site, blood counts, and body mass index. It is simple to use and has been validated in more than 20,000 people in multiple countries, Dr. Carrier said.
In a well-known validation study, Ay et al. showed a VTE complication rate of 10% in patients with a Khorana risk score of 2 or higher who were followed up to 6 months.
“This is huge,” Dr. Carrier stressed. “This is much higher than what we tolerate for all sorts of different populations for which we would recommend anticoagulation or thromboprophylaxis.”
The question is whether the risk score can be helpful in a real-world clinic setting, he said, adding: “I’d like to think the answer to that is yes.”
In the University of Ottawa cohort study, 11% of high-risk patients experienced a VTE complication, compared with 4% of those with lower risk, suggesting that the validation data for the Khorana risk score is not only accurate, it is “actually applicable in real-world practice, and you can use it in your own center,” he said.
Further, recent studies have demonstrated that treatment based on Khorana risk score assessment reduces VTE complications.
Prophylaxis options
Low-molecular-weight heparin (LMWH) has been shown in several studies to be associated with a significant relative VTE risk reduction in patients with cancer initiating chemotherapy – with only a slight, nonsignificant increase in the risk of major bleeding.
However, the absolute benefit was small, and LMWH is “parenteral, relatively costly, and, based on that, although we showed relatively good risk-benefit ratio, it never really got translated to clinical practice,” Dr. Carrier said.
In fact, a 2015 American Society of Clinical Oncology guidelines update recommended against routine thromboprophylaxis in this setting, but stated that it could be considered in select high-risk patients identified using a validated risk-assessment tool.
The guidelines noted that “individual risk factors such as biomarkers and cancer site don’t reliably identify high-risk patients.”
More recent data provide additional support for risk assessment and treatment based on Khorana risk score of 2 or higher.
The AVERT trial, for which Dr. Carrier was the first author, showed that the direct-acting oral anticoagulant (DOAC) apixaban reduced VTE incidence, compared with placebo, in patients with Khorana score of 2 or higher (4.2% vs. 10.2%; hazard ratio, 0.41 overall, and 1.0 vs. 7.3; HR, 0.14 on treatment), and the CASSINI trial showed that another DOAC, rivaroxaban, reduced VTE incidence, compared with placebo, in those with Khorana score of 2 or higher (5.9 vs. 6.7; HR, 0.6 overall, and 2.6 vs. 6.4; HR, 0.40 on treatment). The differences in the on-treatment populations were statistically significant.
The two trials, which included a variety of tumor types, showed similar rates of major bleeding, with an absolute difference of about 1% between treatment and placebo, which was not statistically significant in the on-treatment analyses (HR, 1.89 in AVERT and HR, 1.96 in CASSINI).
A systematic review of these trials showed an overall significant decrease in VTE complication risk with treatment in high-risk patients, and a nonstatistically significant major bleeding risk increase.
Based on these findings, ASCO guidelines were updated in 2020 to state that “routine thromboprophylaxis should not be offered to all patients with cancer. ... However, high-risk outpatients with cancer may be offered thromboprophylaxis with apixaban, rivaroxaban or LMWH, providing there are no significant risk factors for bleeding or drug-drug interactions, and after having a full discussion with patients ... to make sure they understand the risk-benefit ratio and the rationale for that particular recommendation,” he said.
Real-world implementation
Implementing this approach in the clinic setting requires a practical model, such as the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) program, a prospective quality improvement research initiative developed in collaboration with the Jeffords Institute for Quality at the University of Vermont Medical Center and described in a recent report, Dr. Carrier said.
The “Vermont model” is “really a comprehensive model that includes identifying patients with the electronic medical records, gathering the formal education and insight from other health care providers like pharmacists and nurses in order to really come up with personalized care for your patients,” he explained.
In 918 outpatients with cancer who were included in the program, VTE awareness increased from less than 5% before VTEPACC to nearly 82% during the implementation phase and 94.7% after 2 years, with nearly 94% of high-risk patients receiving VTE prophylaxis at that time.
“So we can certainly do that in our own center.” he said. “It’s a matter of coming up with the model and making sure that the patients are seen at the right time.”
Given the high frequency of VTE in patients with cancer initiating chemotherapy, the usefulness of risk scores such as the Khorana risk score for identifying those at high risk, and the availability of safe and effective interventions for reducing risk, “we should probably use the data and incorporate them into clinical practice by implementation of programs for primary prevention,” he said.
A word of caution
Caution is warranted, however, when it comes to using DOACs in patients with higher-risk or potentially higher-risk tumor types, he added.
“It’s an important question we are facing as clinicians on a daily basis,” he said, responding to an attendee’s query, as shared by session moderator James Douketis, MD, professor of medicine at McMaster University, Hamilton, Ont., regarding possible bleeding risks in certain genitourinary cancers.
A recent meta-analysis published in Nature, for example, noted that, in the SELECT-D trial, rivaroxaban was associated with significantly higher incidence of clinically relevant nonmajor bleeding, most often in bladder and colorectal cancers, and most often at genitourinary and gastrointestinal sites.
Both Dr. Carrier and fellow panelist Michael Streiff, MD, professor of medicine at Johns Hopkins University and medical director at the Johns Hopkins Hospital Special Coagulation Laboratory, Baltimore, said they approach DOAC use cautiously, but don’t rule it out entirely, in patients with unresected genitourinary tumors that could pose a risk of bleeding.
“It’s worth mentioning and being cautious. In my own personal practice, I’m very careful with unresected urothelial-type tumors or, for example, bladder cancer, for the same reason as [with] unresected luminal GI tumors,” Dr. Carrier said, adding that he’s also mindful that patients with nephropathy were excluded from U.S. DOAC trials because of bleeding risk.
He said he sometimes tries a LMWH challenge first in higher-risk patients, and then might try a DOAC if no bleeding occurs.
“But it certainly is controversial,” he noted.
Dr. Streiff added that he also worries less with genitourinary cancers than with upper GI lesions because “the signals weren’t as big as in GI” cancers, but he noted that “the drugs are going out through the kidneys ... so I’m cautious in those populations.”
“So caution, but not complete exclusion, is the operative management,” Dr. Douketis said, summarizing the panelists’ consensus.
Dr. Carrier reported clinical trial or advisory board participation for Bayer, Pfizer, Servier, Leo Pharma, and/or BMS.
Primary thromboprophylaxis is feasible and worth considering for high-risk ambulatory patients with cancer who are initiating systemic chemotherapy, according to Marc Carrier, MD.
Risk scores can identify patients at high risk for venous thromboembolism (VTE), and treatments that are effective and associated with low bleeding risk are available, Dr. Carrier explained at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
However, caution is advised in patients with certain types of cancer, including some gastrointestinal and genitourinary cancers, because of the possibility of increased major and clinically relevant nonmajor bleeding risk, he said.
VTE and cancer
VTE is relatively rare in the general population, occurring in about 1 or 2 per 1,000 people annually. The risk increases 4.1-fold in patients with cancer, and 6.5-fold in patients with cancer receiving chemotherapy.
“So just putting these numbers together, we’re no longer talking about 1 in 1,000, but 1 in 200, so [this is] something that is very common among cancer patients,” said Dr. Carrier, a professor at the University of Ottawa and chief of the division of hematology at The Ottawa Hospital.
The mortality rate associated with cancer-associated thrombosis is about 9%, comparable to that associated with infection in the cancer outpatient setting, which underscores the importance of educating patients about the signs and symptoms of VTE so they can seek medical treatment quickly if necessary, he added.
It may also be useful to discuss prophylaxis or other ways to prevent venous thromboembolic complications with certain patients, he said, noting that in an observational cohort study of nearly 600 patients at the University of Ottawa, 25% of those initiating chemotherapy were identified as intermediate or high risk using the validated Khorana risk score, and thus would likely benefit from thromboprophylaxis.
Risk assessment
The Khorana risk score assesses VTE risk based on cancer site, blood counts, and body mass index. It is simple to use and has been validated in more than 20,000 people in multiple countries, Dr. Carrier said.
In a well-known validation study, Ay et al. showed a VTE complication rate of 10% in patients with a Khorana risk score of 2 or higher who were followed up to 6 months.
“This is huge,” Dr. Carrier stressed. “This is much higher than what we tolerate for all sorts of different populations for which we would recommend anticoagulation or thromboprophylaxis.”
The question is whether the risk score can be helpful in a real-world clinic setting, he said, adding: “I’d like to think the answer to that is yes.”
In the University of Ottawa cohort study, 11% of high-risk patients experienced a VTE complication, compared with 4% of those with lower risk, suggesting that the validation data for the Khorana risk score is not only accurate, it is “actually applicable in real-world practice, and you can use it in your own center,” he said.
Further, recent studies have demonstrated that treatment based on Khorana risk score assessment reduces VTE complications.
Prophylaxis options
Low-molecular-weight heparin (LMWH) has been shown in several studies to be associated with a significant relative VTE risk reduction in patients with cancer initiating chemotherapy – with only a slight, nonsignificant increase in the risk of major bleeding.
However, the absolute benefit was small, and LMWH is “parenteral, relatively costly, and, based on that, although we showed relatively good risk-benefit ratio, it never really got translated to clinical practice,” Dr. Carrier said.
In fact, a 2015 American Society of Clinical Oncology guidelines update recommended against routine thromboprophylaxis in this setting, but stated that it could be considered in select high-risk patients identified using a validated risk-assessment tool.
The guidelines noted that “individual risk factors such as biomarkers and cancer site don’t reliably identify high-risk patients.”
More recent data provide additional support for risk assessment and treatment based on Khorana risk score of 2 or higher.
The AVERT trial, for which Dr. Carrier was the first author, showed that the direct-acting oral anticoagulant (DOAC) apixaban reduced VTE incidence, compared with placebo, in patients with Khorana score of 2 or higher (4.2% vs. 10.2%; hazard ratio, 0.41 overall, and 1.0 vs. 7.3; HR, 0.14 on treatment), and the CASSINI trial showed that another DOAC, rivaroxaban, reduced VTE incidence, compared with placebo, in those with Khorana score of 2 or higher (5.9 vs. 6.7; HR, 0.6 overall, and 2.6 vs. 6.4; HR, 0.40 on treatment). The differences in the on-treatment populations were statistically significant.
The two trials, which included a variety of tumor types, showed similar rates of major bleeding, with an absolute difference of about 1% between treatment and placebo, which was not statistically significant in the on-treatment analyses (HR, 1.89 in AVERT and HR, 1.96 in CASSINI).
A systematic review of these trials showed an overall significant decrease in VTE complication risk with treatment in high-risk patients, and a nonstatistically significant major bleeding risk increase.
Based on these findings, ASCO guidelines were updated in 2020 to state that “routine thromboprophylaxis should not be offered to all patients with cancer. ... However, high-risk outpatients with cancer may be offered thromboprophylaxis with apixaban, rivaroxaban or LMWH, providing there are no significant risk factors for bleeding or drug-drug interactions, and after having a full discussion with patients ... to make sure they understand the risk-benefit ratio and the rationale for that particular recommendation,” he said.
Real-world implementation
Implementing this approach in the clinic setting requires a practical model, such as the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTEPACC) program, a prospective quality improvement research initiative developed in collaboration with the Jeffords Institute for Quality at the University of Vermont Medical Center and described in a recent report, Dr. Carrier said.
The “Vermont model” is “really a comprehensive model that includes identifying patients with the electronic medical records, gathering the formal education and insight from other health care providers like pharmacists and nurses in order to really come up with personalized care for your patients,” he explained.
In 918 outpatients with cancer who were included in the program, VTE awareness increased from less than 5% before VTEPACC to nearly 82% during the implementation phase and 94.7% after 2 years, with nearly 94% of high-risk patients receiving VTE prophylaxis at that time.
“So we can certainly do that in our own center.” he said. “It’s a matter of coming up with the model and making sure that the patients are seen at the right time.”
Given the high frequency of VTE in patients with cancer initiating chemotherapy, the usefulness of risk scores such as the Khorana risk score for identifying those at high risk, and the availability of safe and effective interventions for reducing risk, “we should probably use the data and incorporate them into clinical practice by implementation of programs for primary prevention,” he said.
A word of caution
Caution is warranted, however, when it comes to using DOACs in patients with higher-risk or potentially higher-risk tumor types, he added.
“It’s an important question we are facing as clinicians on a daily basis,” he said, responding to an attendee’s query, as shared by session moderator James Douketis, MD, professor of medicine at McMaster University, Hamilton, Ont., regarding possible bleeding risks in certain genitourinary cancers.
A recent meta-analysis published in Nature, for example, noted that, in the SELECT-D trial, rivaroxaban was associated with significantly higher incidence of clinically relevant nonmajor bleeding, most often in bladder and colorectal cancers, and most often at genitourinary and gastrointestinal sites.
Both Dr. Carrier and fellow panelist Michael Streiff, MD, professor of medicine at Johns Hopkins University and medical director at the Johns Hopkins Hospital Special Coagulation Laboratory, Baltimore, said they approach DOAC use cautiously, but don’t rule it out entirely, in patients with unresected genitourinary tumors that could pose a risk of bleeding.
“It’s worth mentioning and being cautious. In my own personal practice, I’m very careful with unresected urothelial-type tumors or, for example, bladder cancer, for the same reason as [with] unresected luminal GI tumors,” Dr. Carrier said, adding that he’s also mindful that patients with nephropathy were excluded from U.S. DOAC trials because of bleeding risk.
He said he sometimes tries a LMWH challenge first in higher-risk patients, and then might try a DOAC if no bleeding occurs.
“But it certainly is controversial,” he noted.
Dr. Streiff added that he also worries less with genitourinary cancers than with upper GI lesions because “the signals weren’t as big as in GI” cancers, but he noted that “the drugs are going out through the kidneys ... so I’m cautious in those populations.”
“So caution, but not complete exclusion, is the operative management,” Dr. Douketis said, summarizing the panelists’ consensus.
Dr. Carrier reported clinical trial or advisory board participation for Bayer, Pfizer, Servier, Leo Pharma, and/or BMS.
FROM THE THSNA BIENNIAL SUMMIT
Factor XI inhibitor–based anticoagulation strategies gain ground
according to Jeffrey I. Weitz, MD.
These strategies could pick up where direct-acting oral anticoagulants leave off, he suggested during a presentation at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
“We all know that the direct oral anticoagulants – the DOACs – are an advance over vitamin K antagonists,” said Dr. Weitz, professor of medicine and biochemistry at McMaster University, Hamilton, Ontario.
Not only are DOACs at least as effective as vitamin K antagonists such as warfarin for stroke prevention in atrial fibrillation or for treatment of venous thromboembolism (VTE), but they also reduce intracranial bleeding and major bleeding risk in those settings, respectively, and they are more convenient to administer because they can be delivered using fixed doses without the need for coagulation monitoring, he added.
Still, new targets are needed, he said, explaining that, although DOACs moved closer to the goal of attenuating thrombosis without increasing the risk of bleeding, annual rates of major bleeding remain at 2%-3% in the atrial fibrillation population, and rates of major and clinically relevant nonmajor bleeding are about 10%.
“The fear of bleeding leads to underuse of anticoagulants for eligible patients with atrial fibrillation and inappropriate use of low-dose [non–vitamin K antagonist oral anticoagulant] regimens, which can leave patients unprotected from thrombotic complications,” he said.
Factor XI
That’s where Factor XI (FXI) may come in, Dr. Weitz said.
Current anticoagulants target enzymes, including FXa or thrombin, in the common pathway of coagulation, but the intrinsic pathway at the level of FXI and FXII has attracted attention in recent years.
The intrinsic pathway is activated when blood comes into contact with medical devices like stents, mechanical heart valves, or central venous catheters, but evidence also suggests that it plays a role in clot stabilization and growth, he explained, noting additional evidence of attenuation of thrombosis in mice deficient in FXI or FXII and in animals with FXI or FXII inhibitors.
“There is no bleeding with congenital FXII deficiency, and patients with FXI deficiency rarely have spontaneous bleeding, although they can bleed with surgery or trauma,” he noted. “Therefore, the promise of contact pathway inhibition is that we can attenuate thrombosis with little or no disruption of hemostasis.”
The initiators of the intrinsic pathway are naturally occurring polyphosphates that can activate FXI and FXII, promote platelet activation, and lead to thrombosis. A number of agents are being investigated to target these enzymes – particularly FXI, for which the strongest epidemiological and other evidence of its link with thrombosis exists. He noted that FXI deficiency appears protective against deep-vein thrombosis (DVT) and ischemic stroke, whereas high levels are linked with an increased risk of venous and arterial thrombosis.
Investigative strategies include the use of antisense oligonucleotides to reduce hepatic synthesis of FXI, aptamers to bind FXI and block its activity, antibodies to bind FXI and block its activation or activity, and small molecules to bind reversibly to the active site of FXI and block its activity “much like the DOACs block the activity of FXa or thrombin.”
“We have to remember that the DOACs have taken over from vitamin K antagonists, like warfarin, for many indications, and as they go generic their uptake will increase even further,” Dr. Weitz said. “When we compare the FXI inhibitors with existing anticoagulants, we don’t necessarily want to go up against the DOACs – we’re looking for indications where [DOACs] have yet to be tested or may be unsafe.”
Potential indications include the following:
Prevention of major adverse cardiovascular events in patients with end-stage renal disease with or without atrial fibrillation.
Provision of a safer platform for antiplatelet therapy in patients with acute coronary syndrome.
Secondary stroke prevention.
Prevention or treatment of cancer-associated VTE.
Prevention of thrombosis associated with central venous catheters, left ventricular assist devices, or mechanical heart valves.
Agents in development
Of the FXI inhibitors in development, ISIS-FXIRx, an antisense oligonucleotide against FXI, is furthest along. In a study published in Blood, ISIS-FXIRx produced a dose-dependent and sustained reduction in FXI levels in healthy volunteers, and in a later randomized study published in The New England Journal of Medicine, it significantly reduced the incidence of DVT in patients undergoing voluntary total knee arthroplasty (30.4% with enoxaparin vs. 4.2% with ISIS-FXIRx at a dose of 300 mg). Bleeding rates were 8.3% and 2.6%, respectively.
The findings showed the potential for reducing thrombosis without increasing bleeding by targeting FXI, Dr. Weitz said, adding that ISIS-FXIRx was also evaluated in a small study of patients with end-stage renal disease undergoing hemodialysis and was shown to produce a dose-dependent reduction in FXI levels and to reduce the incidence of category 3 and 4 clotting in the air trap and dialyzer, compared with placebo, when given in addition to heparin.
This suggests that FXI knockdown can attenuate device-associated clotting to a greater extent than heparin alone, Dr. Weitz said.
The FXIa-directed inhibitory antibody osocimab has also been evaluated in both healthy volunteers and in patients undergoing total knee arthroplasty. In a 2019 study of healthy volunteers, a single IV injection showed a dose-dependent pharmacokinetic profile and produced FXI inhibition for about 1 month, and in the FOXTROT trial published in January in JAMA by Dr. Weitz and colleagues, osocimab was shown to reduce the incidence of symptomatic VTE, asymptomatic DVT, and VTE-related death up to day 10-13 after total knee arthroplasty.
Osocimab at doses ranging from 0.3-1.8 mg/kg given postoperatively or preoperatively were noninferior to enoxaparin (rates of 15.7%-23.7% vs. 26.3%), and osocimab at a preoperative dose of 1.8 mg/kg was superior to both enoxaparin and apixaban (11.5% vs. 26.3% and 14.5%, respectively), he said.
Bleeding rates ranged from 0%-5% with osocimab, compared with 6% with enoxaparin and 2% with apixaban
Ongoing studies
Currently ongoing studies of FXI-directed anticoagulation strategies include a study comparing ISIS-FXIRx with placebo in 200 patients with end-stage renal disease, a study comparing osocimab with placebo in 600 patients with end-stage renal disease, and a study comparing abelacimab – an antibody that binds to FXI and prevents its activation by either FXIIa or thrombin, with enoxaparin in 700 patients undergoing total knee arthroplasty, Dr. Weitz said.
Additionally, there is “considerable activity” with small molecule inhibitors of FXIa, including a phase 2, placebo-controlled, dose-ranging study looking at the novel JNG-7003/BMS-986177 agent for secondary stroke/transient ischemic attack prevention in 2,500 patients and a phase 2 study comparing it with enoxaparin for postoperative thromboprophylaxis in 1,200 patients undergoing total knee arthroplasty.
Parallel phase 2 studies are also underway to compare the novel BAY-2433334 small molecule inhibitor with placebo for stroke/transient ischemic attack prevention, with apixaban for atrial fibrillation, and for prevention of major adverse cardiovascular events in patients with acute MI.
These ongoing trials will help determine the risk-benefit profile of FXI inhibitors he said.
Session comoderator Anne Rose, PharmD, pharmacy coordinator at the University of Wisconsin, Madison, noted that these types of agents have been discussed “for quite some time” and asked whether they will be available for use in clinical practice in the near future.
Dr. Weitz predicted it will be at least a few years. The studies are just now moving to phase 2b and will still need to be evaluated in phase 3 trials and for appropriate new indications, he said.
Dr. Weitz reported research support from Canadian Institutes of Health research, Heart and Stroke Foundation, and Canadian Fund for Innovation, and he is a consultant and/or scientific advisory board member for Anthos, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Pfizer, Portola, Servier , and Thetherex.
according to Jeffrey I. Weitz, MD.
These strategies could pick up where direct-acting oral anticoagulants leave off, he suggested during a presentation at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
“We all know that the direct oral anticoagulants – the DOACs – are an advance over vitamin K antagonists,” said Dr. Weitz, professor of medicine and biochemistry at McMaster University, Hamilton, Ontario.
Not only are DOACs at least as effective as vitamin K antagonists such as warfarin for stroke prevention in atrial fibrillation or for treatment of venous thromboembolism (VTE), but they also reduce intracranial bleeding and major bleeding risk in those settings, respectively, and they are more convenient to administer because they can be delivered using fixed doses without the need for coagulation monitoring, he added.
Still, new targets are needed, he said, explaining that, although DOACs moved closer to the goal of attenuating thrombosis without increasing the risk of bleeding, annual rates of major bleeding remain at 2%-3% in the atrial fibrillation population, and rates of major and clinically relevant nonmajor bleeding are about 10%.
“The fear of bleeding leads to underuse of anticoagulants for eligible patients with atrial fibrillation and inappropriate use of low-dose [non–vitamin K antagonist oral anticoagulant] regimens, which can leave patients unprotected from thrombotic complications,” he said.
Factor XI
That’s where Factor XI (FXI) may come in, Dr. Weitz said.
Current anticoagulants target enzymes, including FXa or thrombin, in the common pathway of coagulation, but the intrinsic pathway at the level of FXI and FXII has attracted attention in recent years.
The intrinsic pathway is activated when blood comes into contact with medical devices like stents, mechanical heart valves, or central venous catheters, but evidence also suggests that it plays a role in clot stabilization and growth, he explained, noting additional evidence of attenuation of thrombosis in mice deficient in FXI or FXII and in animals with FXI or FXII inhibitors.
“There is no bleeding with congenital FXII deficiency, and patients with FXI deficiency rarely have spontaneous bleeding, although they can bleed with surgery or trauma,” he noted. “Therefore, the promise of contact pathway inhibition is that we can attenuate thrombosis with little or no disruption of hemostasis.”
The initiators of the intrinsic pathway are naturally occurring polyphosphates that can activate FXI and FXII, promote platelet activation, and lead to thrombosis. A number of agents are being investigated to target these enzymes – particularly FXI, for which the strongest epidemiological and other evidence of its link with thrombosis exists. He noted that FXI deficiency appears protective against deep-vein thrombosis (DVT) and ischemic stroke, whereas high levels are linked with an increased risk of venous and arterial thrombosis.
Investigative strategies include the use of antisense oligonucleotides to reduce hepatic synthesis of FXI, aptamers to bind FXI and block its activity, antibodies to bind FXI and block its activation or activity, and small molecules to bind reversibly to the active site of FXI and block its activity “much like the DOACs block the activity of FXa or thrombin.”
“We have to remember that the DOACs have taken over from vitamin K antagonists, like warfarin, for many indications, and as they go generic their uptake will increase even further,” Dr. Weitz said. “When we compare the FXI inhibitors with existing anticoagulants, we don’t necessarily want to go up against the DOACs – we’re looking for indications where [DOACs] have yet to be tested or may be unsafe.”
Potential indications include the following:
Prevention of major adverse cardiovascular events in patients with end-stage renal disease with or without atrial fibrillation.
Provision of a safer platform for antiplatelet therapy in patients with acute coronary syndrome.
Secondary stroke prevention.
Prevention or treatment of cancer-associated VTE.
Prevention of thrombosis associated with central venous catheters, left ventricular assist devices, or mechanical heart valves.
Agents in development
Of the FXI inhibitors in development, ISIS-FXIRx, an antisense oligonucleotide against FXI, is furthest along. In a study published in Blood, ISIS-FXIRx produced a dose-dependent and sustained reduction in FXI levels in healthy volunteers, and in a later randomized study published in The New England Journal of Medicine, it significantly reduced the incidence of DVT in patients undergoing voluntary total knee arthroplasty (30.4% with enoxaparin vs. 4.2% with ISIS-FXIRx at a dose of 300 mg). Bleeding rates were 8.3% and 2.6%, respectively.
The findings showed the potential for reducing thrombosis without increasing bleeding by targeting FXI, Dr. Weitz said, adding that ISIS-FXIRx was also evaluated in a small study of patients with end-stage renal disease undergoing hemodialysis and was shown to produce a dose-dependent reduction in FXI levels and to reduce the incidence of category 3 and 4 clotting in the air trap and dialyzer, compared with placebo, when given in addition to heparin.
This suggests that FXI knockdown can attenuate device-associated clotting to a greater extent than heparin alone, Dr. Weitz said.
The FXIa-directed inhibitory antibody osocimab has also been evaluated in both healthy volunteers and in patients undergoing total knee arthroplasty. In a 2019 study of healthy volunteers, a single IV injection showed a dose-dependent pharmacokinetic profile and produced FXI inhibition for about 1 month, and in the FOXTROT trial published in January in JAMA by Dr. Weitz and colleagues, osocimab was shown to reduce the incidence of symptomatic VTE, asymptomatic DVT, and VTE-related death up to day 10-13 after total knee arthroplasty.
Osocimab at doses ranging from 0.3-1.8 mg/kg given postoperatively or preoperatively were noninferior to enoxaparin (rates of 15.7%-23.7% vs. 26.3%), and osocimab at a preoperative dose of 1.8 mg/kg was superior to both enoxaparin and apixaban (11.5% vs. 26.3% and 14.5%, respectively), he said.
Bleeding rates ranged from 0%-5% with osocimab, compared with 6% with enoxaparin and 2% with apixaban
Ongoing studies
Currently ongoing studies of FXI-directed anticoagulation strategies include a study comparing ISIS-FXIRx with placebo in 200 patients with end-stage renal disease, a study comparing osocimab with placebo in 600 patients with end-stage renal disease, and a study comparing abelacimab – an antibody that binds to FXI and prevents its activation by either FXIIa or thrombin, with enoxaparin in 700 patients undergoing total knee arthroplasty, Dr. Weitz said.
Additionally, there is “considerable activity” with small molecule inhibitors of FXIa, including a phase 2, placebo-controlled, dose-ranging study looking at the novel JNG-7003/BMS-986177 agent for secondary stroke/transient ischemic attack prevention in 2,500 patients and a phase 2 study comparing it with enoxaparin for postoperative thromboprophylaxis in 1,200 patients undergoing total knee arthroplasty.
Parallel phase 2 studies are also underway to compare the novel BAY-2433334 small molecule inhibitor with placebo for stroke/transient ischemic attack prevention, with apixaban for atrial fibrillation, and for prevention of major adverse cardiovascular events in patients with acute MI.
These ongoing trials will help determine the risk-benefit profile of FXI inhibitors he said.
Session comoderator Anne Rose, PharmD, pharmacy coordinator at the University of Wisconsin, Madison, noted that these types of agents have been discussed “for quite some time” and asked whether they will be available for use in clinical practice in the near future.
Dr. Weitz predicted it will be at least a few years. The studies are just now moving to phase 2b and will still need to be evaluated in phase 3 trials and for appropriate new indications, he said.
Dr. Weitz reported research support from Canadian Institutes of Health research, Heart and Stroke Foundation, and Canadian Fund for Innovation, and he is a consultant and/or scientific advisory board member for Anthos, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Pfizer, Portola, Servier , and Thetherex.
according to Jeffrey I. Weitz, MD.
These strategies could pick up where direct-acting oral anticoagulants leave off, he suggested during a presentation at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
“We all know that the direct oral anticoagulants – the DOACs – are an advance over vitamin K antagonists,” said Dr. Weitz, professor of medicine and biochemistry at McMaster University, Hamilton, Ontario.
Not only are DOACs at least as effective as vitamin K antagonists such as warfarin for stroke prevention in atrial fibrillation or for treatment of venous thromboembolism (VTE), but they also reduce intracranial bleeding and major bleeding risk in those settings, respectively, and they are more convenient to administer because they can be delivered using fixed doses without the need for coagulation monitoring, he added.
Still, new targets are needed, he said, explaining that, although DOACs moved closer to the goal of attenuating thrombosis without increasing the risk of bleeding, annual rates of major bleeding remain at 2%-3% in the atrial fibrillation population, and rates of major and clinically relevant nonmajor bleeding are about 10%.
“The fear of bleeding leads to underuse of anticoagulants for eligible patients with atrial fibrillation and inappropriate use of low-dose [non–vitamin K antagonist oral anticoagulant] regimens, which can leave patients unprotected from thrombotic complications,” he said.
Factor XI
That’s where Factor XI (FXI) may come in, Dr. Weitz said.
Current anticoagulants target enzymes, including FXa or thrombin, in the common pathway of coagulation, but the intrinsic pathway at the level of FXI and FXII has attracted attention in recent years.
The intrinsic pathway is activated when blood comes into contact with medical devices like stents, mechanical heart valves, or central venous catheters, but evidence also suggests that it plays a role in clot stabilization and growth, he explained, noting additional evidence of attenuation of thrombosis in mice deficient in FXI or FXII and in animals with FXI or FXII inhibitors.
“There is no bleeding with congenital FXII deficiency, and patients with FXI deficiency rarely have spontaneous bleeding, although they can bleed with surgery or trauma,” he noted. “Therefore, the promise of contact pathway inhibition is that we can attenuate thrombosis with little or no disruption of hemostasis.”
The initiators of the intrinsic pathway are naturally occurring polyphosphates that can activate FXI and FXII, promote platelet activation, and lead to thrombosis. A number of agents are being investigated to target these enzymes – particularly FXI, for which the strongest epidemiological and other evidence of its link with thrombosis exists. He noted that FXI deficiency appears protective against deep-vein thrombosis (DVT) and ischemic stroke, whereas high levels are linked with an increased risk of venous and arterial thrombosis.
Investigative strategies include the use of antisense oligonucleotides to reduce hepatic synthesis of FXI, aptamers to bind FXI and block its activity, antibodies to bind FXI and block its activation or activity, and small molecules to bind reversibly to the active site of FXI and block its activity “much like the DOACs block the activity of FXa or thrombin.”
“We have to remember that the DOACs have taken over from vitamin K antagonists, like warfarin, for many indications, and as they go generic their uptake will increase even further,” Dr. Weitz said. “When we compare the FXI inhibitors with existing anticoagulants, we don’t necessarily want to go up against the DOACs – we’re looking for indications where [DOACs] have yet to be tested or may be unsafe.”
Potential indications include the following:
Prevention of major adverse cardiovascular events in patients with end-stage renal disease with or without atrial fibrillation.
Provision of a safer platform for antiplatelet therapy in patients with acute coronary syndrome.
Secondary stroke prevention.
Prevention or treatment of cancer-associated VTE.
Prevention of thrombosis associated with central venous catheters, left ventricular assist devices, or mechanical heart valves.
Agents in development
Of the FXI inhibitors in development, ISIS-FXIRx, an antisense oligonucleotide against FXI, is furthest along. In a study published in Blood, ISIS-FXIRx produced a dose-dependent and sustained reduction in FXI levels in healthy volunteers, and in a later randomized study published in The New England Journal of Medicine, it significantly reduced the incidence of DVT in patients undergoing voluntary total knee arthroplasty (30.4% with enoxaparin vs. 4.2% with ISIS-FXIRx at a dose of 300 mg). Bleeding rates were 8.3% and 2.6%, respectively.
The findings showed the potential for reducing thrombosis without increasing bleeding by targeting FXI, Dr. Weitz said, adding that ISIS-FXIRx was also evaluated in a small study of patients with end-stage renal disease undergoing hemodialysis and was shown to produce a dose-dependent reduction in FXI levels and to reduce the incidence of category 3 and 4 clotting in the air trap and dialyzer, compared with placebo, when given in addition to heparin.
This suggests that FXI knockdown can attenuate device-associated clotting to a greater extent than heparin alone, Dr. Weitz said.
The FXIa-directed inhibitory antibody osocimab has also been evaluated in both healthy volunteers and in patients undergoing total knee arthroplasty. In a 2019 study of healthy volunteers, a single IV injection showed a dose-dependent pharmacokinetic profile and produced FXI inhibition for about 1 month, and in the FOXTROT trial published in January in JAMA by Dr. Weitz and colleagues, osocimab was shown to reduce the incidence of symptomatic VTE, asymptomatic DVT, and VTE-related death up to day 10-13 after total knee arthroplasty.
Osocimab at doses ranging from 0.3-1.8 mg/kg given postoperatively or preoperatively were noninferior to enoxaparin (rates of 15.7%-23.7% vs. 26.3%), and osocimab at a preoperative dose of 1.8 mg/kg was superior to both enoxaparin and apixaban (11.5% vs. 26.3% and 14.5%, respectively), he said.
Bleeding rates ranged from 0%-5% with osocimab, compared with 6% with enoxaparin and 2% with apixaban
Ongoing studies
Currently ongoing studies of FXI-directed anticoagulation strategies include a study comparing ISIS-FXIRx with placebo in 200 patients with end-stage renal disease, a study comparing osocimab with placebo in 600 patients with end-stage renal disease, and a study comparing abelacimab – an antibody that binds to FXI and prevents its activation by either FXIIa or thrombin, with enoxaparin in 700 patients undergoing total knee arthroplasty, Dr. Weitz said.
Additionally, there is “considerable activity” with small molecule inhibitors of FXIa, including a phase 2, placebo-controlled, dose-ranging study looking at the novel JNG-7003/BMS-986177 agent for secondary stroke/transient ischemic attack prevention in 2,500 patients and a phase 2 study comparing it with enoxaparin for postoperative thromboprophylaxis in 1,200 patients undergoing total knee arthroplasty.
Parallel phase 2 studies are also underway to compare the novel BAY-2433334 small molecule inhibitor with placebo for stroke/transient ischemic attack prevention, with apixaban for atrial fibrillation, and for prevention of major adverse cardiovascular events in patients with acute MI.
These ongoing trials will help determine the risk-benefit profile of FXI inhibitors he said.
Session comoderator Anne Rose, PharmD, pharmacy coordinator at the University of Wisconsin, Madison, noted that these types of agents have been discussed “for quite some time” and asked whether they will be available for use in clinical practice in the near future.
Dr. Weitz predicted it will be at least a few years. The studies are just now moving to phase 2b and will still need to be evaluated in phase 3 trials and for appropriate new indications, he said.
Dr. Weitz reported research support from Canadian Institutes of Health research, Heart and Stroke Foundation, and Canadian Fund for Innovation, and he is a consultant and/or scientific advisory board member for Anthos, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Pfizer, Portola, Servier , and Thetherex.
FROM THE THSNA BIENNIAL SUMMIT