Medical Oncology Unit, Fondazione Policlinico A. Gemelli IRCCS. Largo Agostino Gemelli 8, 00168 Rome, Italy.
Medical Oncology Unit, Fondazione Policlinico A. Gemelli IRCCS. Largo Agostino Gemelli 8, 00168 Rome, Italy.
Cancer Treat Rev. 2022 Apr;105:102379. doi: 10.1016/j.ctrv.2022.102379. Epub 2022 Mar 12.
The recent approval of immune checkpoint inhibitor (ICI)-based combinations has redefined the first-line standard of care of metastatic renal cell carcinoma (mRCC) patients. Although the undisputed advantage of these combinations, most patients progressed, requiring subsequent therapies. The change of first-line therapy inevitably led to modification of the all mRCC treatment algorithm; to date, the most appropriate second-line options remain still unclear. The aim of our review was to provide a useful summary of the available evidence in order to overcome the doubts about treatment sequences. Retrospectively, the efficacy of second-line VEGFR-TKIs seems to be greater after failure of a dual ICIs combination rather than after ICIs plus VEGFR-TKIs, nevertheless prospective data of second-line TKIs are limited. Moreover, ICI re-challenge could be an option but, again, most data derived from retrospective series emphasizing the identification of predictive factors of response to select mRCC patients that could benefit from this strategy. Novel molecules and different ICI-based combinations are under evaluation with the aim of implementing the second-line setting. In particular, belzutifan, ciforadenant (CPI-444), and talazoparib achieved encouraging objective response rates (ORR) in phase I/II trials. Phase III trials comparing these new molecules with the standard of care are currently ongoing. The first-line regimen, and the type and duration of response emerged as crucial factors that could influence the efficacy of second-line therapy. Prognostic models that integrate clinical features and molecular biomarkers with a predictive value are warranted to guide clinicians in the decision-making process with the ultimate goal of offering to the patients the most effective therapy in a personalized, precision medicine-based, therapeutic strategy.
最近，免疫检查点抑制剂（ICI）联合治疗方案的获批重新定义了转移性肾细胞癌（mRCC）患者的一线标准治疗。尽管这些联合治疗方案具有不可否认的优势，但大多数患者仍会进展，需要后续治疗。一线治疗的改变不可避免地导致了所有 mRCC 治疗方案的改变；迄今为止，最合适的二线选择仍不清楚。我们的综述旨在提供可用证据的有用总结，以消除对治疗顺序的疑虑。回顾性研究表明，在双重 ICI 联合治疗失败后，二线 VEGFR-TKI 的疗效似乎优于 ICI 联合 VEGFR-TKI 治疗失败后，尽管二线 TKI 的前瞻性数据有限。此外，ICI 再挑战可能是一种选择，但同样，大多数数据来自回顾性系列，强调了识别对该策略有反应的预测因素的重要性，以选择可能从中受益的 mRCC 患者。新型分子和不同的 ICI 联合治疗方案正在评估中，目的是在二线治疗中实施。特别是，belzutifan、ciforadenant（CPI-444）和 talazoparib 在 I/II 期试验中取得了令人鼓舞的客观缓解率（ORR）。目前正在进行这些新分子与标准治疗比较的 III 期试验。一线治疗方案、反应类型和持续时间是影响二线治疗疗效的关键因素。需要整合具有预测价值的临床特征和分子生物标志物的预后模型，以指导临床医生做出决策，最终目标是在个性化、精准医学为基础的治疗策略中为患者提供最有效的治疗。
