Petrelli Fausto, Vavassori Ivano, Rossitto Mauro, Dottorini Lorenzo
Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy.
Urology Unit, ASST Bergamo Ovest, 24047 Treviglio, BG, Italy.
Cancers (Basel). 2024 Jul 20;16(14):2598. doi: 10.3390/cancers16142598.
There is a significant gap in the literature concerning the effective management of second-line therapy for patients with metastatic renal cell carcinoma (RCC) who have received immune checkpoint inhibitors (ICIs). Most of the published articles were small multicenter series or phase 2 studies. To our knowledge, a systematic review that comprehensively outlines the range of treatment options available for patients with metastatic RCC who do not respond to first-line ICIs has not yet been conducted. Our aim was to synthesize evidence on second-line therapies for patients with metastatic RCC after initial treatment with ICIs and to offer recommendations on the best treatment regimens based on the current literature.
We conducted a search in PubMed, Embase, and the Cochrane Library on 29 February 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We selected articles that met the predetermined inclusion criteria (written in English, retrospective observational studies, prospective series, and randomized trials reporting second-line therapy for metastatic RCC after failure of ICI-based therapy). Relevant articles were identified in the reference lists. The main endpoint was the overall response rate (ORR), with the median progression-free survival (PFS) and overall survival (OS) as secondary endpoints.
We included 27 studies reporting the outcomes of 1970 patients. Salvage therapies were classified as targeted therapy (VEGFR TKIs) in 18 studies and ICIs in 8 studies. In studies where TKIs were the second line of choice, the pooled ORR was 34% (95% CI: 30.2-38%). In studies where ICIs, alone or in combination with TKIs, were used as second-line therapies, the ORR was 25.7% (95% CI: 15.7-39.2%). In studies where TKIs and ICIs were the second-line choices, the pooled median PFS values were 11.4 months (95% CI: 9.5-13.6 months) and 9.8 months (95% CI: 7.5-12.7 months), respectively.
This systematic review shows that VEGFR TKIs and ICIs are effective second-line therapies following an initial treatment with anti-PD(L)1 alone or in combination. The treatment choice should be personalized, taking into account the patient's response to first-line ICIs, the site of the disease, the type of first-line combination (with or without VEGFR TKIs), and the patient's overall condition.
在接受免疫检查点抑制剂（ICI）治疗的转移性肾细胞癌（RCC）患者二线治疗的有效管理方面，文献中存在显著差距。大多数已发表的文章是小型多中心系列研究或2期研究。据我们所知，尚未进行过系统综述全面概述对一线ICI无反应的转移性RCC患者可用的治疗选择范围。我们的目的是综合关于ICI初始治疗后转移性RCC患者二线治疗的证据，并根据当前文献就最佳治疗方案提供建议。
我们于2024年2月29日按照系统评价和Meta分析的首选报告项目（PRISMA）指南在PubMed、Embase和Cochrane图书馆进行了检索。我们选择符合预定纳入标准的文章（用英文撰写、回顾性观察研究、前瞻性系列研究以及报告基于ICI治疗失败后转移性RCC二线治疗的随机试验）。在参考文献列表中识别相关文章。主要终点是总缓解率（ORR），次要终点是无进展生存期（PFS）中位数和总生存期（OS）。
我们纳入了27项报告1970例患者结局的研究。挽救性治疗在18项研究中被分类为靶向治疗（VEGFR TKIs），在8项研究中为ICI。在以TKIs作为二线选择的研究中，汇总的ORR为34%（95%CI：30.2 - 38%）。在将ICI单独或与TKIs联合用作二线治疗的研究中，ORR为25.7%（95%CI：15.7 - 39.2%）。在以TKIs和ICI作为二线选择的研究中，汇总的PFS中位数分别为11.4个月（95%CI：9.5 - 13.6个月）和9.8个月（95%CI：7.5 - 12.7个月）。
这项系统综述表明，VEGFR TKIs和ICI是单独或联合使用抗PD（L）1初始治疗后的有效二线治疗方法。治疗选择应个体化，考虑患者对一线ICI的反应、疾病部位、一线联合类型（有无VEGFR TKIs）以及患者的总体状况。
