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

Background: New safety concerns of the 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 updated drug labels of TAAs several years after their initial regulatory approval and whether their emergence can be predicted. Methods: Updated drug labels of TAAs agents 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 updated drug labels. Generalized linear mixed models were used to examine 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 biomarkers. Time was a significant predictor of new WPs (p ˂ 0.001) and BWs (p = 0.008). Updated drug labels of small molecules received significantly more new WPs (p = 0.042) as compared to monoclonal antibodies. The availability of companion diagnostics for 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 changing risk-benefit ratios of approved TAAs.