Overall Survival Benefits of Cancer Drugs Approved in China From 2005 to 2020

Abstract

Importance: 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.

Objective: 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.

Main outcomes and measures: 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.

Results: 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%]).

Conclusions and relevance: 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.

Figure 1.. Timeline of Landmark Legislation and Regulations Relating to China’s Drug Administration

Landmark policies above the timeline were issued by the National Medical Products Administration (NMPA) (also called State Food and Drug Administration [SFDA] and previously the China Food and Drug Administration [CFDA]). Policies below the timeline were issued by the State Council. See eTable 1 in the Supplement for more details of the policies. R&D indicates research and development.

Figure 2.. First Marketing Authorization and Supplemental Indication Approval Time of Cancer Drugs Authorized in China Between 2005 and 2020

A, Cancer drugs approved in China only and cancer drugs also approved by the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) by December 31, 2020. B, Indications for solid tumors or hematological malignant neoplasms.