New Serious Safety Warnings for Targeted Anticancer Agents After Their Initial FDA Approval

Background: New safety concerns about targeted anticancer agents (TAAs) often emerge in the first few years after their initial regulatory approval. Our aim was to determine whether new serious and potentially fatal adverse drug reactions (ADRs) continue to emerge in the updated drug labels of TAAs several years after their initial regulatory approval and whether their emergence can be predicted. Methods: The updated drug labels of TAAs approved by the U.S. Food and Drug Administration before July 2013 were analyzed. Serious and potentially fatal ADRs were identified in the Warnings & Precautions (WPs) and Boxed Warnings (BWs) sections of the updated drug labels. Generalized linear mixed models were used to examine the associations between the number of adverse drug reactions and time, drug type (small molecules vs. monoclonal antibodies), and the availability of companion diagnostics for biomarkers. Results: Among 37 eligible TAAs, 25 (68%) were small molecules and 11 (30%) had available companion diagnostics for the biomarkers. Time was a significant predictor of new WPs (p ˂ 0.001) and BWs (p = 0.008). The updated drug labels of the small molecules received significantly more new WPs (p = 0.042) as compared to monoclonal antibodies. The availability of the companion diagnostics for the biomarkers did not have an impact on the emergence of new ADRs. Conclusions: New serious ADRs of TAAs continue to emerge in updated drug labels several years after their initial regulatory approval. Oncologists, regulators, and payers should be aware of the changing risk–benefit ratios of approved TAAs.