Liang Zhizhou, Yang Yu, Zhang Yichen, Han Kexin, Li Huangqianyu, Shi Luwen, Guan Xiaodong
Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Haidian District, #38 Xueyuan Road, Beijng, China.
School of Nursing, University of Hong Kong, Hong Kong, China.
Invest New Drugs. 2025 Aug 22. doi: 10.1007/s10637-025-01560-5.
Previous research shows that the benefits of phase-I oncology trials increased from 5 to 18% between 2000 and 2019 globally. However, the risk-benefit profile of phase-I trials in China is unclear. This study aims to analyze the risk-benefit profile of phase-I oncology trials in China and explore their correlation. We included adult phase-I oncology trials registered on the Chinese Clinical Trial Registry and Information Disclosure Platform between September 2013 and December 2021. Data on response rates and grade-3/4 adverse events were retrieved from PubMed, Google Scholar, and CNKI to assess their correlation. A total of 189 trials with 9591 patients were analyzed. The median response rate was 25.4% (IQR, 9.4-41.4%), and the overall incidence of grade-3/4 adverse events was 29.3% (IQR, 15.0-43.8%). No significant trends were observed over time. Subgroup analysis showed higher response rates in lymphoma (45.8%), cell therapies (80.0%), and biomarker trials (38.0%). Higher adverse event rates were seen in breast cancer (55.0%), chemical drugs (33.3%), cytotoxic drugs (73.3%), and combination therapies (35.7%). A weak correlation was found between response rates and grade-3/4 adverse events (ρ = 0.217; p = 0.003), with a moderate correlation in immunotherapy (ρ = 0.417; p < 0.001). This is the first assessment of early efficacy and safety signals of phase-I oncology trials in China. No significant temporal trends were identified. However, the correlation in immunotherapy suggests that higher benefits may be accompanied by greater risks.
先前的研究表明，2000年至2019年期间，全球I期肿瘤试验的效益从5%提高到了18%。然而，中国I期试验的风险效益情况尚不清楚。本研究旨在分析中国I期肿瘤试验的风险效益情况，并探讨它们之间的相关性。我们纳入了2013年9月至2021年12月在中国临床试验注册与信息公示平台上注册的成人I期肿瘤试验。从PubMed、谷歌学术和中国知网检索了缓解率和3/4级不良事件的数据，以评估它们之间的相关性。共分析了189项试验，涉及9591名患者。中位缓解率为25.4%（四分位间距，9.4-41.4%），3/4级不良事件的总体发生率为29.3%（四分位间距，15.0-43.8%）。未观察到随时间的显著趋势。亚组分析显示，淋巴瘤（45.8%）、细胞疗法（80.0%）和生物标志物试验（38.0%）的缓解率较高。乳腺癌（55.0%）、化学药物（33.3%）、细胞毒性药物（73.3%）和联合疗法（35.7%）的不良事件发生率较高。缓解率与3/4级不良事件之间存在弱相关性（ρ = 0.217；p = 0.003），免疫疗法中存在中度相关性（ρ = 0.417；p < 0.001）。这是对中国I期肿瘤试验早期疗效和安全性信号的首次评估。未发现显著的时间趋势。然而，免疫疗法中的相关性表明，更高的效益可能伴随着更大的风险。
