Background: The proven efficacy of mTOR inhibitors (mTORIs), tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma (RCC) suggests that these agents should be investigated as adjuvant therapy with the aim of eliminating undetectable microscopic residual disease after curative resection. The aim of our study was to compare the efficacy of these treatments using an innovative method of reconstructing individual patient data. Methods: Nine phase III trials describing adjuvant RCC treatments were selected. The IPDfromKM method was used to reconstruct individual patient data from Kaplan–Meier (KM) curves. The combination treatments were compared with the control arm (placebo) for disease-free survival (DFS). Multi-treatment KM curves were used to summarize the results. Standard statistical tests were performed. These included hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population, the study showed that two ICIs (nivolumab plus ipilimumab and pembrolizumab) and one TKI (sunitinib) were superior to the placebo, whereas both TKIs and mTORIs were inferior. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown. Conclusions: This novel approach to investigating survival has allowed us to conduct all indirect head-to-head comparisons between these agents in a context where no “real” comparative trials have been conducted.
背景：mTOR抑制剂（mTORIs）、酪氨酸激酶抑制剂（TKIs）或免疫检查点抑制剂（ICIs）在转移性肾细胞癌（RCC）中已证实的疗效表明，应将这些药物作为辅助疗法进行研究，以消除根治性切除后无法检测到的微观残留病灶。本研究旨在通过一种创新的个体患者数据重建方法，比较这些治疗方案的疗效。方法：选取了九项描述RCC辅助治疗的III期临床试验。采用IPDfromKM方法从Kaplan-Meier（KM）曲线重建个体患者数据。将联合治疗方案与对照组（安慰剂）在无病生存期（DFS）方面进行比较。使用多治疗KM曲线总结结果，并进行了标准统计检验，包括风险比和异质性似然比检验。结果：在总体人群中，研究表明两种ICIs（纳武利尤单抗联合伊匹木单抗以及帕博利珠单抗）和一种TKI（舒尼替尼）优于安慰剂，而TKIs和mTORIs均劣于安慰剂。由于我们评估DFS作为辅助治疗比较的主要终点，总体生存获益仍未知。结论：这种研究生存期的新方法使我们能够在尚未进行“真实”比较试验的情况下，对这些药物进行所有间接的头对头比较。
肿瘤(癌症)患者之家