基于免疫检查点抑制剂联合方案一线治疗晚期或转移性肾细胞癌的网状Meta分析

Immune checkpoint inhibitor combinations as first-line therapy in advanced or metastatic renal cell carcinoma: a network Meta-analysis

摘要

目的: 系统评价基于免疫检查点抑制剂(immune checkpoint inhibitors,ICI)的不同联合方案一线治疗晚期或转移性肾细胞癌(renal cell carcinoma,RCC)的疗效和安全性,为临床治疗选择提供依据。方法: 计算机检索PubMed、The Cochrane Library、Embase、Web of Science、中国知网及万方数据库,收集关于ICI一线治疗晚期或转移性RCC的随机对照临床试验(randomized controlled trial,RCT),检索时限为建库至2025年1月30日。由2名研究者独立筛选文献、提取资料和评估研究的偏倚风险,采用R 4.5.0软件进行网状Meta分析。结果: 共纳入7项RCT,涉及8种治疗措施。网状Meta分析结果显示,在总生存期(overall survival,OS)方面,ICI联合方案中,阿替利珠单抗联合贝伐珠单抗和纳武利尤单抗联合伊匹木单抗之间存在统计学差异,其他联合方案间无显著差异;累积排序概率显示,特瑞普利单抗联合阿昔替尼成为最佳方案的概率最高。在无进展生存期(progression-free survival,PFS)方面,仑伐替尼联合帕博利珠单抗表现最优,其疾病进展风险显著低于阿替利珠单抗联合贝伐珠单抗、阿维鲁单抗联合阿昔替尼、纳武利尤单抗联合伊匹木单抗和帕博利珠单抗联合阿昔替尼等方案。在客观缓解率(objective response rate,ORR)方面,纳武利尤单抗联合卡博替尼和仑伐替尼联合帕博利珠单抗表现最佳,显著优于帕博利珠单抗联合阿昔替尼等方案。在安全性方面,纳武利尤单抗联合伊匹木单抗和阿替利珠单抗联合贝伐珠单抗方案≥3级治疗相关不良事件(treatment-related adverse events,TRAE)风险显著低于其他联合方案,但这两组间无显著差异。结论: 在晚期或转移性RCC一线治疗中,基于ICI的联合治疗方案在疗效上普遍优于传统靶向治疗药物舒尼替尼。不同联合方案之间的比较显示,在OS方面大多数未观察到统计学显著差异;然而在PFS、ORR及TRAE方面,部分方案间存在显著差异。研究方案的相对优劣未来有待通过更多头对头研究进一步证实。

Abstract

Objective: To systematically evaluate the efficacy and safety of different combination regimens based on immune checkpoint inhibitors (ICI) as first-line treatment for advanced or metastatic renal cell carcinoma (RCC), and provide evidence for clinical treatment selection. Methods: A comprehensive search of electronic databases was conducted, including PubMed, The Cochrane Library, Embase, Web of Science, CNKI, and Wanfang Data from inception until January 30, 2025, for relevant randomized controlled trial (RCT). After literature screening, data extraction, and risk of bias assessment for the included studies were performed independently by two investigators, a network Meta-analysis was performed using R software version 4.5.0. Results: A total of seven RCT involving eight treatment interventions were included. Network Meta-analysis results showed that for overall survival (OS), a statistically significant difference was observed only between atezolizumab plus bevacizumab and nivolumab plus ipilimumab, with no significant differences detected among other regimen comparisons. Cumulative ranking probabilities indicated that toripalimab plus axitinib had the highest probability of being the most effective regimen for OS. Regarding progression-free survival (PFS), lenvatinib plus pembrolizumab was identified as the most effective intervention. It demonstrated a statistically significant reduction in the risk of disease progression compared to several other regimens, including atezolizumab plus bevacizumab, avelumab plus axitinib, nivolumab plus ipilimumab, and pembrolizumab plus axitinib. For objective response rate (ORR), nivolumab plus cabozantinib and lenvatinib plus pembrolizumab were associated with higher ORR, with both showing significant superiority to regimens such as pembrolizumab plus axitinib. In terms of safety, the incidence of grade ≥3 treatment-related adverse events (TRAE) was significantly lower with nivolumab plus ipilimumab and atezolizumab plus bevacizumab compared to the other combination regimens. However, no statistically significant difference in TRAE was found between them. Conclusion: In the first-line treatment of advanced or metastatic RCC, ICI combination regimens generally demonstrated superior efficacy compared to sunitinib. No statistically significant differences in OS were observed for most comparisons between the combination regimens. However, statistically significant differences were detected among specific regimens in terms of PFS, ORR, and TRAE. Their relative rankings need further confirmation through more head-to-head studies in the future.

关键词

免疫检查点抑制剂 / 肾细胞癌 / 一线治疗 / 网状Meta分析

Key words

immune checkpoint inhibitors / renal cell carcinoma / first-line treatment / network Meta-analysis

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