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

Abstract

ABSTRACT Background Hundreds of cancer drugs are approved globally based on surrogate endpoint response rate (RR). However, the characteristics of RR‐based approvals remain unknown. Methods 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. Results 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%. Conclusions 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.

Keywords

• accelerated approval
• cancer drug
• regular approval
• response rate
• surrogate endpoint