Evaluation of anticancer therapy-related dermatologic adverse events: Insights from Food and Drug Administration's Adverse Event Reporting System dataset.

Abstract

New anticancer therapies have improved patient outcomes but associated dermatologic adverse events (AEs) may cause morbidity and treatment discontinuation. A comprehensive estimation of associations between cancer drugs and skin AEs is lacking. This study utilized the Food and Drug Administartion (FDA)'s Adverse Event Reporting System database (January 2013-September 2022), with 3,399,830 reports involving 3084 drugs and 16,348 AEs. A nearest neighbor matching model was employed to select 10 controls for each case report, utilizing the cosine similarity of demographic and AE severity factors to minimize false positives/negatives. There were 10,698 unique anticancer drugs (n = 212) to skin AE (n = 873) pairs, of which 676 had significant reporting odds ratios (ROR) > 1, comprising 113 drugs and 144 AEs. The minimum ROR was 1.25, and 50% of associations displayed a ROR >10. The most common were rash (51 agents) and dry skin (28 drugs). Methotrexate induced the most distinct AEs (34), then mechlorethamine (33), and vemurafenib (24). Targeted therapies accounted for 49% of pairs, cytotoxic chemotherapies for 35.9%, and immunotherapies for 11%. A total of 113 anticancer drugs were identified as significantly associated with skin AEs, most frequently rash and dry skin. Data are likely under-reported but enable quick postmarketing identification of skin toxicity signals.