Surrogate endpoints have supported the majority of oncology drug approvals in the United States in recent history, particularly for indications in the third- or later-line settings, according to findings presented at the 2023 ASCO Annual Meeting.

“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),” said Akshit Chitkara, MD, University of California Riverside, and coauthors. “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.”

The retrospective analysis involved US oncology approvals from 2006 to 2022. The findings build upon previous research conducted by Dr Chitkara and coinvestigators, which included approvals up to 2017. For the analysis, researchers looked at FDA documents, package inserts, and clinical trial data related to each approval.

“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,” researchers said. “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…were all included within the OS category.”

Less than one-third (29%; 98 of 342) of approved indications relied on definite endpoints, while 71% (244 of 342) were based on surrogate endpoints, according to the findings. RR and PFS were used in 37% (127 of 342) and 34% (117 of 342) of approvals, respectively.

Surrogate endpoints, which included disease-free survival, objective response rate, metabolic complete response rate, and other outcomes in addition to PFS and RR, were used in all lines of therapy. Researchers identified the greatest trend toward using surrogate endpoints for approvals in the third- or later-line settings (88%; 38 of 43), followed by second-line (74%; 102 of 138) and then first-line (63%; 91 of 145).

“FDA commonly accepts surrogate endpoints as criteria for drug approval in oncology since 2006. There is a tradeoff between providing access to cancer therapies and potentially approving therapies that still have unverified clinical benefits,” researchers advised.
 

Reference:
Chitkara A, Rai MP, Thawani R, Chen EY. Recent analysis of frequency of surrogate end points used in oncology clinical trials 2006-2022. J Clin Oncol. 2023;41(suppl 16; abstr e13658). doi:10.1200/JCO.2023.41.16_suppl.e13658