e13658 Background: Surrogate endpoints expedite the clinical trial results at the cost of more uncertainty with clinical efficacy, as they may have a weak correlation with definite endpoints like overall survival (OS). Increased use of surrogate measures such as progression-free survival (PFS) and response rate (RR) are increasingly used by the FDA for drug registration trials in oncology. We conducted this analysis to update our previous analysis (2006-2017) and to study the recent trends in using these surrogate endpoints for approval by FDA. We also study how these surrogate markers are used across various therapy lines. Methods: Our retrospective analysis of US FDA oncology approvals from 2006 to 2022 examined FDA documents from the FDA website, package inserts, and related published trials. Only drug approvals for non-hematologic solid tumors were included. We collected data about the approval type, conversion to regular approval, drug withdrawals (until February 11, 2022), lines of therapy (first-line, second-line, and third or other lines), and endpoints used for FDA approval. All surrogate endpoints were categorized into response rate (RR), generally a proportion, or progression-free survival (PFS), a time-to-event endpoint. Definite endpoints, including patient-reported outcomes (PRO), were all included within the OS category. Results: We identified that OS/PRO endpoints accounted for only 29% (98 of 342) of drug indication approvals. In contrast, 71% of drug approvals (244 of 342) were based on surrogate endpoints; 37% (127 of 342) of drug indications used RR endpoints, followed by 34% (117 of 342) drug indications that used PFS endpoints. These surrogate endpoints (RR, PFS, CR, DFS, EFS, pCR, iDFS, MCR, MFS, ORR, RFS, rPFS combined) showed a trend toward being used in the third- or later-line line setting followed by second-line (91 of 145 drug indications [63%] for first-line vs. 102 of 138 drug indications [74%] for second-line vs. 38 of 43 drug indications [88%] for third- or later-line). Still, they were used in all lines of therapy. Conclusions: FDA commonly accepts surrogate endpoints as criteria for drug approval in oncology since 2006. There has been a trend toward using surrogate endpoints in the third or later lines of drug approvals by the FDA. There is a tradeoff between providing access to cancer therapies and potentially approving therapies that still have unverified clinical benefits.