Cardiovascular warnings common but slower to be issued for FDA-approved cancer drugs
Although more than 25% of contemporary FDA-approved cancer therapies required cardiovascular warnings, post-marketing issuance of the warnings trailed clinical approval by several years, according to a research letter in JAMA Oncology.
“Our findings suggest the need for increased vigilance to potentially limit cardiotoxic events, such as arrhythmias. This is especially important as many patients with cancer are anticipated to survive well beyond their initial months of diagnosis and treatment,” Daniel Addison, MD, assistant professor of medicine and director of the cardio-oncology program at The Ohio State University Comprehensive Cancer Center, told Healio.
Investigators pooled data from an FDA database and public FDA drug reviews on all cancer therapies and biologics awarded new drug applications by the agency between 1998 and 2018. They assessed characteristics related to approval drug class, therapeutic area, priority review status, accelerated approval status, orphan drug status, regulatory review times, near-regulatory deadline approval status, and the presence or absence of preceding early-phase trial reports of cardiotoxic effects. Drug characteristics associated with the need for and timing of safety communications were also evaluated with multivariable stepwise backward-selection logistic regression.
Researchers identified 125 FDA-approved cancer therapies, among which 82 were biologics, targeted or immune-based therapies.
Overall, 411 post-marketing safety communications were issued, including 33 black box warnings, seven withdrawals, 24 dose-adjustment warnings and 347 general warnings or precautions. Of note, 40.3% of targeted and immune therapies received a cardiovascular disease warning.
Cardiovascular disease was the most common reason for any black box warning (37.2%), with sudden death prompting 11.6% of black box warnings.
Immune-based or targeted therapies and those within classes with prior reported cardiotoxic events were more likely to require black box warnings (OR = 1.99; 95% CI, 0.22-0.99). Common reasons for cardiovascular disease warnings included arrhythmias (23.5%), uncontrolled hypertension (12.1%), heart failure (11.4%) and sudden death (3.2%).
Moreover, 24 therapies (21.6%) had multiple cardiovascular toxic effects warnings. Myocarditis was associated with only two therapies.
Thirty-two cancer therapies (25.6%) had post-marketing cardiac safety communications, of which seven (33.3%) were new black box warnings. Compared with a median time of 1,120 days for the issuance of noncardiac warnings, median time to issuance of a cardiac warning was 1,670 days (P = .03).
“Cardiotoxicity warnings significantly lag other types of warnings issued by the FDA for cancer therapies, and arrhythmic warnings occur much later than heart failure or hypertension,” Addison said. “It would be interesting to understand if there is a shift in the pattern of cardiotoxicity warnings issued during the next 2 to 5 years by the FDA and others. We are increasingly appreciating the cost of cardiotoxicity among patients with cancer. This is something that patients and clinicians are looking for and we are developing strategies to evaluate this.”
For more information:
Daniel Addison, MD, can be reached at The Ohio State University Comprehensive Cancer Center, 460 W 10th Ave., Columbus, OH 43210; email: daniel.addison@osumc.edu.
Collapse