Cancer Drugs Approved Based on Surrogate Endpoint: A Retrospective Observational Study in the United States and China

Hundreds of cancer drugs are approved globally based on surrogate endpoint response rate (RR). However, the characteristics of RR-based approvals remain unknown.

In this retrospective study, all cancer drug-indication pairs approved based on RR in the United States and China up to December 2023 were analyzed.

A total of 249 RR-supported drug-indication pairs were identified in the United States and 98 in China. In the United States, 98 of the 249 (39.4%) indications were granted regular approval (RA), whereas in China, only 21 of 98 (21.4%) approvals followed this regulatory pathway, with the remainder receiving accelerated approval (AA). The conversion rate from AA to RA was significantly lower in China compared to the United States (13.3% vs. 28.1%, p < 0.001). The proportion of AA withdrawals was significantly lower in China compared to the United States (1.0% vs. 10.4%, p < 0.001). Among all indications, the median RR in China was 60.9% (IQR, 35.8%-75.0%), which was significantly higher than the 45.0% (IQR, 29.0%-61.0%) in the United States (p < 0.001). In China, 18 of the 98 (18.4%) had an RR less than 30%. In contrast, in the United States, 26.9% of the 249 had an RR less than 30%.

Compared to the United States, RR-supported approvals in China are characterized by higher RR values and a stricter RA pathway. Regulatory authorities in both countries may need to consider both the quantity and quality during cancer drug development based on surrogate endpoints.