Roviello Giandomenico, Andre Fabrice, Venturini Sergio, Pistilli Barbara, Curigliano Giuseppe, Cristofanilli Massimo, Rosellini Pietro, Generali Daniele
Medical Oncology Unit, Department of Oncology, San Donato Hospital, Via Nenni 20, 52100 Arezzo, Italy; Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy.
Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Eur J Cancer. 2017 Nov;86:257-265. doi: 10.1016/j.ejca.2017.09.018. Epub 2017 Oct 19.
To assess the role of the tumour response rate (RR) after immune checkpoint inhibitors-based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors-based treatments.
The systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome.
Twenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R = 0.47; 95% confidence interval [CI], 0.03-0.77; P = 0.001; and R = 0.32; 95% CI, 0.02-0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non-small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte-associated antigen 4 checkpoint inhibitors.
The results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors.
为了评估基于免疫检查点抑制剂的治疗后肿瘤缓解率（RR）作为实体瘤患者无进展生存期（PFS）和总生存期（OS）潜在替代终点的作用，我们对比较不同基于免疫检查点抑制剂治疗的随机研究进行了基于试验的Meta回归分析。
系统文献检索包括电子数据库和肿瘤学会议论文集。对PFS和OS的治疗效果以风险比（HRs）表示；对RR的治疗效果以优势比（ORs）表示。对经对数转换的治疗效果估计值进行加权回归分析，以检验替代结局的治疗效果与临床结局的治疗效果之间的关联。
分析纳入了24项试验，共11894例患者。使用完整数据集，RR的log(OR)对PFS的log(HR)或OS的log(HR)的回归显示出弱关联（R = 0.47；95%置信区间[CI]，0.03 - 0.77；P = 0.001；以及R = 0.32；95%CI，0.02 - 0.76；P = 0.01）。根据不同疾病类型和免疫检查点抑制剂不同作用机制对试验进行分层的预先计划分析显示，RR与非小细胞肺癌的OS之间存在非常弱的关联，而RR与细胞毒性T淋巴细胞相关抗原4检查点抑制剂的PFS之间存在适度关联。
基于试验的Meta回归分析结果表明RR与OS之间存在弱相关性，支持未来开展研究以评估RR在接受免疫检查点抑制剂治疗患者中的替代作用。
