Iskander Renata, Moyer Hannah, Fergusson Dean, McGrath Sean, Benedetti Andrea, Kimmelman Jonathan
Department of Equity, Ethics and Policy, McGill University, Montreal, Quebec, Canada (R.I., H.M., J.K.).
Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada (D.F.).
Ann Intern Med. 2024 Jun;177(6):759-767. doi: 10.7326/M23-2515. Epub 2024 Apr 30.
Many patients participate in cancer trials to access new therapies. The extent to which new treatments produce clinical benefit for trial participants is unclear.
To estimate the progression-free survival (PFS) and overall survival (OS) advantage of assignment to experimental groups in randomized trials for 6 solid tumors.
ClinicalTrials.gov was searched for trials of investigational drugs with results posted between 2017 and 2021.
Investigational drugs were defined as those not yet having full approval from the U.S. Food and Drug Administration for the study indication. Trials were included if they were randomized and tested drugs or biologics.
Data extraction was completed by 2 independent reviewers. Data were pooled using a random-effects model.
The sample included 128 trials comprising 141 comparisons of a new drug and a comparator. These comparisons included 47 050 patients. The pooled hazard ratio for PFS was 0.80 (95% CI, 0.75 to 0.85), indicating statistically significant benefit for patients in experimental groups. This corresponded to a median PFS advantage of 1.25 months (CI, 0.80 to 1.68 months). The pooled hazard ratio for OS was 0.92 (CI, 0.88 to 0.95), corresponding to a survival gain of 1.18 months (CI, 0.72 to 1.71 months). The absolute risk for a serious adverse event for comparator group patients was 29.56% (CI, 26.64% to 32.65%), with an increase in risk of 7.40% (CI, 5.66% to 9.14%) for patients in experimental groups.
Trials in this sample were heterogeneous. Comparator group interventions were assumed to reflect standard of care.
Assignment to experimental groups produces statistically significant survival gains. However, the absolute survival gain is small, and toxicity is statistically significantly greater. The findings of this review provide reassuring evidence that patients are not meaningfully disadvantaged by assignment to comparator groups.
Canadian Institutes of Health Research.
许多患者参与癌症试验以获取新疗法。新疗法对试验参与者产生临床益处的程度尚不清楚。
评估6种实体瘤随机试验中分配至试验组的无进展生存期（PFS）和总生存期（OS）优势。
检索ClinicalTrials.gov上2017年至2021年间公布结果的研究性药物试验。
研究性药物定义为尚未获得美国食品药品监督管理局对研究适应症完全批准的药物。试验若为随机且测试药物或生物制品则纳入。
由2名独立评审员完成数据提取。使用随机效应模型汇总数据。
样本包括128项试验，包含141次新药与对照药的比较。这些比较涉及47050名患者。PFS的合并风险比为0.80（95%CI，0.75至0.85），表明试验组患者有统计学显著益处。这相当于PFS中位数优势为1.25个月（CI，0.80至1.68个月）。OS的合并风险比为0.92（CI，0.88至0.95），对应生存期增加1.18个月（CI，0.72至1.71个月）。对照药组患者发生严重不良事件的绝对风险为29.56%（CI，26.64%至32.65%），试验组患者风险增加7.40%（CI，5.66%至9.14%）。
本样本中的试验具有异质性。假定对照药组干预措施反映了标准治疗。
分配至试验组可产生统计学显著的生存期获益。然而，绝对生存期获益较小，且毒性在统计学上显著更大。本综述结果提供了令人安心的证据，即患者被分配至对照药组并无明显劣势。
加拿大卫生研究院。
