| Autor: |
Xingxian Luo, Xin Du, Lin Huang, Qixiang Guo, Xufeng Lv, Cen Wang, Haopeng Liu, Yue Zhou, Xuecai Xue, Zhuangqi Li, Jingwen Liu, Shein-Chung Chow, Yue Yang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
EClinicalMedicine, Vol 63, Iss , Pp 102177- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2589-5370 |
| DOI: |
10.1016/j.eclinm.2023.102177 |
| Popis: |
Summary: Background: Accelerated approval (AA) of novel anticancer drugs based on surrogacy has attracted considerable concern globally. China National Medical Products Administration (NMPA) also established a similar conditional approval (CA) program to accelerate the approval of novel drugs to address unmet medical needs. This cross-sectional study aimed to evaluate the pre-approval clinical trial evidence and potential challenge of cancer drugs receiving CA in China from policy implementation to 2022. Methods: The cancer drugs (initial and supplemental indications) granted CA between January 1, 2015 and December 31, 2022 using the public database of the NMPA were analyzed. The characteristics of the cancer drugs received CA were described. Primary efficacy endpoints and safety derived from the pre-approval clinical trial, including response rates (RR), progression-free survival (PFS), overall survival (OS), treatment-related serious adverse events (SAE) and Grade ≥3 adverse events (AEs) were quantitatively estimated by meta-analysis. Besides, the correlation between the surrogate endpoints and OS was estimated by the reported trial-level correlation analysis. Findings: The NMPA approved 72 cancer indications (56 new molecular entities) with CA between 2015 and 2022. 34 indications (47%) were also approved by the FDA or EMA. 74% (53/72) of cancer indications were based on a single-arm trial design while 26% (19/72) for randomized controlled trials. The pooled RR was 0.50 (95% CI: 0.45–0.55, I2 = 96%) with significant differences across cancer types and targets while the pooled hazard risk was 0.39 (95% CI: 0.28–0.53, I2 = 89%) for PFS and 0.67 (95% CI: 0.61–0.73, I2 = 0%) for OS. The pooled treatment-related SAE and Grade ≥3 AEs from single-arm designs resulted in 15% and 25%, respectively. In randomized controlled trials, the pooled treatment-related SAE and Grade ≥3 AEs observed in CA drugs and the control groups were comparable. Surrogate endpoints were widely used as the primary efficacy endpoints in the pre-approval pivotal clinical trials with 75% (54/72) for RR, 10% (7/72) for PFS, and 4% (3/72) for others. Of these, 27% (17/63) of the surrogate endpoints reported a trial-level correlation with OS; three reported high correlation (r ≥ 0.85), two reported moderate correlation (0.70 ≤ r |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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