2000年至2020年美国食品和药品管理局新型癌症治疗药物批准的证据基础。
The evidence base of US Food and Drug Administration approvals of novel cancer therapies from 2000 to 2020.
发表日期：2023 Feb 13
作者：
Viktoria Gloy, Andreas M Schmitt, Pascal Düblin, Julian Hirt, Cathrin Axfors, Hanna Kuk, Tiago V Pereira, Clara Locher, Laura Caquelin, Martin Walter-Claudi, Mark P Lythgoe, Amanda Herbrand, Benjamin Kasenda, Lars G Hemkens
来源：
INTERNATIONAL JOURNAL OF CANCER
摘要：
有人担心，加速肿瘤药物批准的监管计划可能会增加治疗对生存和生活质量的益处和危害不确定性。我们分析了FDA在2000年至2020年间首次批准的所有肿瘤药物的所有关键临床试验和所有非关键随机对照试验（RCT）。我们报告了监管和试验特征。通过meta分析总结了对总生存期（OS），无进展生存期和肿瘤反应的影响。对QoL的影响进行了定性总结。 FDA在2000年至2020年间基于190次临床试验批准了145种新的抗癌药物，共156种适应症。一半的适应症（49％）没有RCT证据，82％仅有单个临床试验。 OS是14％的试验的主要终点，QoL数据来自25％的试验。中位OS效益为2.55个月（IQR，1.33-4.28），OS的平均风险比为0.75（95％CI为0.72-0.79，I2 = 42）。对于156种适应症，QoL的改善只有7种（4％）进行了报告。随着时间的推移，优先审查越来越受到重视，并且每种适应症的试验数量从1.45下降到1.12。有关QoL的结果报告的试验数量增加（2000-2005年为19％;2016-2020年为41％）。在过去的21年中，新的抗癌药通常是基于一项单一的、常常无控制的临床试验来批准，以测量代表性终点。这使得癌症患者没有可靠的证据表明新药物改善了他们的生存或QoL，也没有表明得到改善。 © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics. Effects on overall survival (OS), progression-free survival and tumor response were summarized in meta-analyses. Effects on QoL were qualitatively summarized. Between 2000 and 2020, the FDA approved 145 novel cancer drugs for 156 indications based on 190 clinical trials. Half of indications (49%) were approved without RCT evidence; 82% had a single clinical trial only. OS was primary endpoint in 14% of trials and QoL data were available from 25%. The median OS benefit was 2.55 months (IQR, 1.33-4.28) with a mean hazard ratio for OS of 0.75 (95%CI, 0.72-0.79, I2 = 42). Improvement for QoL was reported for 7 (4%) of 156 indications. Over time, priority review was used increasingly and the mean number of trials per indication decreased from 1.45 to 1.12. More trials reported results on QoL (19% in 2000-2005; 41% in 2016-2020). For 21 years, novel cancer drugs have typically been approved based on one single, often uncontrolled, clinical trial, measuring surrogate endpoints. This leaves cancer patients without solid evidence that novel drugs improve their survival or QoL and there is no indication towards improvement.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.