Abstract 111P
Background
New safety concerns of targeted anticancer agents often emerge in the first few years after their regulatory approval. However, a long-term trajectory of the emergence of these safety concerns is not known. Here we analyzed updated drug labels of approved targeted anticancer agents for the reporting of late serious ADRs.
Methods
Targeted anticancer agents approved by the U.S. Food and Drugs Administration (FDA) before July 2013 were eligible for our study. For each agent serious ADRs (hereafter ADRs) and potentially fatal ADRs were identified in the Warnings & Precautions (W&P) and Boxed warnings (BW) sections of the FDA updated drug labels. Any new serious ADR first reported in the updated drug label ≥ 5 years after approval of the corresponding anticancer was defined as late ADR. Analysis was stratified by the drug type (small molecule targeted agents [SMs] vs. monoclonal antibodies [mAbs]) and by the availability of the companion diagnostics for biomarkers (yes vs. no).
Results
We analyzed 36 anticancer agents (25 SMs and 11 mAbs). A median time between initial drug approval and the last updated drug label was 11.8 yrs (range 6.8 – 24 yrs). Over time new ADRs appeared in updated labels of 34 (94%) agents. At least one late ADR was reported for 30 (83%) agents. On average, numerically higher number of late ADRs emerged in updated drug labels of SMs as compared to mAbs, respectively (2.4 vs. 1.5; p=0.06). Similarly, updated labels of agents without companion diagnostics for biomarkers, on average, reported numerically higher number of late ADRs (2.3 vs. 1.5; p=0.33). Late potentially fatal ADRs were reported for only 2 (6%) agents.
Conclusions
Serious safety concerns of anticancer agents are often newly reported in updated drug labels more than five years after their regulatory approval. Oncologists prescribing targeted anticancer agents should be vigilant for late ADRs in everyday clinical practice.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
D. Ribnikar: Other, Institutional, Advisory Board: Novartis. B. Seruga: Other, Institutional, Advisory Board: Astellas, Janssen Pharmaceuticals, AstraZeneca. All other authors have declared no conflicts of interest.