LAUSR

Abstract Background U.S. Food and Drug Administration (FDA) approves drugs based on overall survival (OS) in oncology trials in order to speed up access of novel drugs to the market. Methods We examined all adult anticancer drugs approved by the FDA from Jan’2006 to Jan’2019. Data regarding the approval type (regular or accelerated), cancer type, treatment indication, and basis for approval were extracted from the FDA website and any relevant publications. The basis for approval was categorized into the response rate (RR), progression-free survival (PFS), and overall survival (OS) endpoints and their analysis. Approvals for pediatric cancers, biosimilars, and cancers limited to genetic syndromes were not included in this study. Results A total of 258 FDA approvals were analyzed, of which 57 (22.09%) were approved for first-line therapy and 201 (77.91%) for subsequent lines. Sixty-six (25.58%) were approved based on the OS endpoint, 23 (8.91%) in the first line and 43 (16.67%) in the subsequent lines. One hundred ninety-two (74.42%) drugs were granted approval (regular and accelerated) based on surrogate endpoints: 104 (40.31%) of them for RR and 87 (33,72%) for PFS. Thirteen (5.04%) and 91 (35.27%) were approved for RR, and 20 (7.75%) and 67 (25.97%) were approved for PFS in the first and subsequent lines, respectively (Table). Table Out of the total 258 FDA approvals, 66 (25.58%) were accelerated and 192 (74.42%) regular. Ten (3.88%) and 56 (21.71%) obtained accelerated approval in the first and subsequent lines, respectively. Forty-seven (18.22%) and 145 (56.20%) were granted regular approval in the first and subsequent lines, respectively. Table . 486P Lines of treatment # of approvals for RR (%) # of approvals for PFS (%) # of approvals for OS (%) Total # of approvals (%) First line 13 (5.04) 20 (7.75) 23 (8.91) 57 (22.09) Subsequent lines 91 (35.27) 67 (25.97) 43 (16.17) 201 (77.91) Total 104 (40.31) 87 (33.72) 66 (25.58) 258 (100) Conclusions RR and PFS were the most frequently approved surrogate endpoints, most often for use in later lines of therapy. The accelerated approvals based on surrogate endpoints in later lines of therapy represent a topic of current debate. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.