Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
LSE Health, Department of Health Policy, London School of Economics and Political Science, London, United Kingdom.
JAMA Netw Open. 2022 Aug 1;5(8):e2225973. doi: 10.1001/jamanetworkopen.2022.25973.
Of approximately 9 million patients with cancer in China in 2020, more than half were diagnosed with late-stage cancers. Recent regulatory reforms in China have focused on improving the availability of new cancer drugs. However, evidence on the clinical benefits of new cancer therapies authorized in China is not available.
To characterize the clinical benefits of cancer drugs approved in China, as defined by the availability and magnitude of statistically significant overall survival (OS) results.
DESIGN, SETTING, AND PARTICIPANTS: This mixed-methods study comprising a systematic review and cross-sectional analysis identified antineoplastic agents approved in China between January 1, 2005, and December 31, 2020, using publicly available data and regulatory review documents issued by the National Medical Products Administration. The literature published up to June 30, 2021, was reviewed to collect results on end points used in pivotal trials supporting cancer drug approvals.
The primary outcome measure was a documented statistically significant positive OS difference between a new cancer therapy and a comparator treatment. Secondary outcome measures were the magnitude of OS benefit and other primary efficacy measures in pivotal trials.
Between 2005 and 2020, 78 cancer drugs corresponding to 141 indications were authorized in China, including 20 drugs (25.6%) (for 30 indications) approved in China only. Of all indications, 26 (18.4%) were evaluated in single-arm or dose-optimization trials, most of which were authorized after 2017. By June 30, 2021, 34 drug indications (24.1%) had a documented lack of OS gain. For 68 indications (48.2%) that had documented evidence of OS benefit, the median magnitude of OS improvement was 4.1 (range, 1.0-35.0) months. After a median follow-up of 1.9 (range, 1.0-11.1) years from approval, OS data for 13 indications (9.2%) were either not reported or were still not mature. Fewer than one-third of cancer drug indications approved in China only had documented evidence of OS benefits (9 of 30 [30.0%]), whereas more than one-half of the cancer drug indications also available in the US or Europe had OS benefits (59 of 111 [53.1%]).
In this study, almost half of cancer drug indications approved in China had demonstrated OS gain. With the increase of cancer drug approvals based on single-arm trials or immature survival data in recent years, these findings highlight the need to routinely monitor the clinical benefits of new cancer therapies in China.
2020 年中国约有 900 万癌症患者，其中一半以上被诊断为晚期癌症。中国最近的监管改革集中于提高新癌症药物的可及性。然而，关于在中国获得批准的新癌症疗法的临床获益的证据尚不可用。
本混合方法研究通过系统评价和横断面分析，以新的癌症治疗方法与对照治疗方法之间是否存在具有统计学意义的总生存期（OS）差异来确定在中国获得批准的癌症药物的临床获益，以此为特征。
设计、设置和参与者：本研究纳入了 2005 年 1 月 1 日至 2020 年 12 月 31 日期间在中国获得批准的抗肿瘤药物，这是通过公开可用的数据和国家药品监督管理局发布的监管审查文件确定的。对截至 2021 年 6 月 30 日发表的文献进行了综述，以收集支持癌症药物批准的关键性试验中终点的结果。
主要结局指标是新的癌症疗法与对照治疗方法之间存在具有统计学意义的 OS 差异。次要结局指标是关键性试验中 OS 获益的程度和其他主要疗效指标。
2005 年至 2020 年间，中国共批准了 78 种癌症药物，对应 141 种适应证，其中 20 种（25.6%）（30 种适应证）仅在中国获得批准。所有适应证中，26 种（18.4%）采用单臂或剂量优化试验进行评估，其中大多数是在 2017 年后获得批准的。截至 2021 年 6 月 30 日，34 种药物适应证（24.1%）缺乏 OS 获益的证据。对于有 OS 获益证据的 68 种适应证（48.2%），OS 改善的中位数幅度为 4.1 个月（范围，1.0-35.0 个月）。在批准后中位随访 1.9 年（范围，1.0-11.1 年）后，13 种适应证（9.2%）的 OS 数据未报告或仍不成熟。在中国仅获得批准的癌症药物适应证中，仅有 9 种（30.0%）有 OS 获益的证据，而在中国或欧洲也获得批准的癌症药物适应证中，有 59 种（53.1%）有 OS 获益的证据。
在这项研究中，近一半在中国获得批准的癌症药物适应证显示出 OS 获益。近年来，随着基于单臂试验或不成熟生存数据的癌症药物批准数量的增加，这些发现强调了在中国常规监测新癌症疗法临床获益的必要性。
