A systematic analysis of off-label drug use in real-world data (RWD) across more than 145,000 cancer patients.

Abstract

e18031 Background: Off-label drug use is common in cancer treatment (tx) due to limited approved tx options. Systematic analysis of RWD for off-label drug use facilitates hypothesis generation and design of clinical studies for new indications. Methods: We analyzed systemic tx data of > 145,000 cancer patients at Mount Sinai hospitals for 60 chemotherapy, 80 targeted, 16 hormonal therapy drugs, and 6 immune checkpoint inhibitors (CPIs). Off-label use was determined when patients received a drug for cancer indications that had not received regulatory approval, and the tx was not in a clinical trial setting. Clinical response to off-label tx was assessed using time to treatment discontinuation (TTD) as a surrogate endpoint. Results: Chemotherapy drugs were used off-label more frequently than targeted and hormonal agents. Across all cancer tx regimens involving a chemotherapy drug , 31% were off-label. In contrast, for tx regimens involving targeted and hormonal therapy drugs, only 11% and 6.7%, respectively, were used off-label. Further investigation revealed that chemotherapy often combines multiple drugs, where the combinations may include one or more drugs not approved for the disease. For example, cisplatin is approved only for bladder, ovarian and testicular cancers, but is widely used in combination to treat other cancers. Consequently, we observed an 84% off-label use of cisplatin. Several targeted drugs and CPIs were used off-label at high frequencies. 53% of nivolumab tx was off-label, primarily for treating hepatocellular carcinoma (before FDA approval) and relapsed/refractory multiple myelomas (RRMM). Trametinib targeting MEK and venetoclax targeting Bcl-2 were used off-label at a frequency of 84% and 89%, respectively, mainly in RRMM. In MM patients treated with trametinib (n = 91) and venetoclax (n = 121), 14 (15%) and 42 (35%), respectively, had TTD > 120 days. Conclusions: Off-label uses of novel targeted and immunotherapy drugs are likely based on disease mechanisms and when clinical trials deliver early, encouraging results. A thorough chart review would help us better understand clinical response as well as adverse events in these patients and potentially guide future clinical studies.