目的:基于免疫检查点抑制剂(ICI)的联合治疗是转移性肾细胞癌(mRCC)的标准全身治疗。尽管ICI+ICI和ICI+酪氨酸激酶抑制剂(TKI)组合之间的不同药理作用可能会影响结果。使用真实世界数据的比较研究很少。
方法:我们回顾性分析了2018年1月至2023年8月在多个机构接受基于ICI的一线联合治疗的447例mRCC患者的记录,并选择了320例诊断为透明细胞RCC(ccRCC)的患者进行进一步研究。使用基于IMDC风险分类的一对一倾向评分对队列进行匹配。总生存期(OS),无进展生存期(PFS),客观反应率(ORR),和治疗相关的不良事件(TrAE)进行比较。
结果:匹配过程产生了228例接受ICI+ICI(n=114)或ICI+TKI(n=114)治疗的转移性ccRCC患者。ICI+ICI治疗患者的中位OS为53个月(95CI:33-NA),ICI+TKI未达到(95CI:43-NA)(P=0.24)。ICI+ICI的中位PFS显著缩短(13个月,95CI:7-25)比ICI+TKI(25个月,95CI:13-NA)(P=0.047)。ICI+ICI或ICI+TKI一线组合后,序贯治疗的二线PFS无差异(6vs.8个月,P=0.6)。两组之间的ORR没有差异(ICI+ICI:51%vs.ICI+TKI:55%,P=0.8);使用ICI+ICI组合治疗的患者的进行性疾病(PD)率明显更高(24%vs.11%,P=0.029)。在ICI+TKI治疗的患者中,任何级别的TrAE的发生率均显着较高(71%vs.85%,P=0.016),但我们发现两组之间严重的TrAE没有差异(39%vs.36%,P=0.8)。
结论:在匹配的现实世界数据队列中,我们确认了ICI+ICI和ICI+TKI组合的OS获益相当.然而,在PFS方面的不同临床行为,PD率,基于ICI的组合和TrAE之间可能会丰富临床决策。
OBJECTIVE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few.
METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared.
RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8).
CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.