Comparison of treatment efficacy of targeted therapies approved in China for non-small cell lung cancer before and after the introduction of accelerated drug marketing registration procedures.

Abstract

Introduction: The introduction of Accelerated Drug Marketing Registration Procedures (ADMRPs) in China has improved patient access to innovative therapies, but concerns remain about the robustness and consistency of efficacy evidence.

Aim: This study aimed to compare the treatment efficacy of approved targeted therapies for non-small cell lung cancer (NSCLC) before and after the implementation of ADMRPs.

Method: In this retrospective study, we analyzed targeted therapies for NSCLC approved in China as of December 31, 2024. Approvals were categorized as pre-policy or post-policy groups based on the July 1, 2020 implementation of ADMRPs. Descriptive statistics were used to examine approved indications and pivotal trial designs. Meta-analysis and meta-regression compared pre-approval efficacy outcomes, including overall survival (OS), progression-free survival (PFS), disease-free survival, and objective response rate (ORR), between groups. Sensitivity analyses evaluated post-marketing OS data and the robustness of results.

Results: A total of 59 indications supported by 72 trials were approved. Post-policy approvals increased markedly (41 vs 18), with rises in domestic drugs (16.7% pre-policy vs 61.0% post-policy) and uncommon targets (5.6% pre-policy vs 43.9% post-policy) (both P < 0.05). Pivotal trials shifted from primarily Phase III-IV randomized controlled trials (RCTs) (76.0%) pre-policy to Phase I-II single-arm designs (68.1%) post-policy, mainly supporting drugs for uncommon or resistance mutations, whereas approvals for classical targets remained predominantly based on RCTs (90.0% pre-policy vs 93.8% post-policy; P = 0.416). Meta-analyses found no significant differences in pre-approval efficacy between groups for PFS (HR: 0.52 [0.45-0.61] vs 0.44 [0.36-0.54]; P = 0.206) or ORR (0.63 [0.55-0.70] vs 0.65 [0.59-0.70]; P = 0.705). However, OS meta-analysis was only feasible in the pre-policy group, whereas OS data in the post-policy group remained immature, with a median follow-up of 17 months (IQR 8-34) after approval.

Conclusion: After the introduction of ADMRPs, approvals of targeted therapies for NSCLC increased substantially, without significant loss of pre-approval treatment efficacy. However, due to the limited follow-up, definitive survival benefits for the post-policy group cannot yet be established. The increased reliance on single-arm trials underscores the necessity of rigorous confirmatory post-marketing studies.