Rizzo Alessandro, Monteiro Fernando Sabino Marques, Mollica Veronica, Soares Andrey, Brunetti Oronzo, Ricci Angela Dalia, Massari Francesco, Santoni Matteo
S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, Bari, 70124, Italy.
Latin American Cooperative Oncology Group - LACOG, Porto Alegre, RS, Brazil.
Clin Exp Metastasis. 2024 Dec 16;42(1):3. doi: 10.1007/s10585-024-10322-1.
Studies conducted in the last few years have suggested a connection between clinical outcomes and the time of immune checkpoint inhibitors (ICIs) infusion. However, few data are available regarding the differences between early and late time-of-day (ToD) administration in metastatic renal cell carcinoma (mRCC) patients receiving immunotherapy and immune-based combinations. In this meta-analysis, we aimed to fully investigate the influence of timing of administration on the efficacy of mRCC immunotherapy, by comparing early ToD versus late ToD dosing in this setting. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Overall Survival (OS) was measured as Hazard Ratios (HRs) and 95% confidence intervals (CIs). Our search resulted in the identification of 1429 potentially relevant reports, which were subsequently restricted to four following independent evaluation of three authors. The pooled HR for OS in RCC patients receiving early ToD versus late ToD dosing was 0.62 (95% Confidence Interval, 0.50-0.72; p < 0.001). According to our findings, a statistically significant improvement in terms of OS for mRCC patients receiving early ToD administration compared with late ToD dosing was observed, with a reduction of death by 38%. Well-designed, randomized clinical and translational trials are required to clarify this issue and to establish recommendations for personalized treatments according to ToD.
过去几年进行的研究表明临床结果与免疫检查点抑制剂（ICI）输注时间之间存在关联。然而，关于接受免疫治疗和基于免疫的联合治疗的转移性肾细胞癌（mRCC）患者在一天中早期和晚期给药之间的差异，可用数据很少。在这项荟萃分析中，我们旨在通过比较这种情况下一天中早期给药与晚期给药，全面研究给药时间对mRCC免疫治疗疗效的影响。本系统评价和荟萃分析是根据系统评价和荟萃分析的首选报告项目（PRISMA）进行的。总生存期（OS）以风险比（HRs）和95%置信区间（CIs）衡量。我们的检索共识别出1429篇潜在相关报告，随后在三位作者进行独立评估后筛选至四篇。接受一天中早期给药与晚期给药的RCC患者的OS合并HR为0.62（95%置信区间，0.50 - 0.72；p < 0.001）。根据我们的研究结果，观察到与晚期给药相比，接受一天中早期给药的mRCC患者在OS方面有统计学显著改善，死亡风险降低了38%。需要设计良好的随机临床和转化试验来阐明这个问题，并根据给药时间制定个性化治疗建议。
