Division of Medical Oncology, Beth Israel Medical Center, Boston, MA.
Department of Medicine, Beth Israel Medical Center, Boston, MA.
Clin Genitourin Cancer. 2020 Jun;18(3):179-184.e3. doi: 10.1016/j.clgc.2019.11.016. Epub 2019 Dec 5.
Immune checkpoint inhibitors and vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors are the most commonly used medications in metastatic renal cell carcinoma (mRCC). Recently, large clinical trials have shown favorable outcomes in patients treated with combined immune checkpoint plus VEGFR inhibition compared with VEGFR inhibition alone. However, the benefit among favorable risk (based on International Metastatic Renal Cell Carcinoma Database Consortium score) and elderly (age > 65 years) patients was not clear, leading to a discrepancy between United States Food and Drug Administration and European Association of Urology recommendations.
We searched available literature for phase III randomized clinical trials evaluating the efficacy of combining immunotherapy plus VEGF/VEGFR inhibitors versus standard of care in patients with previously untreated mRCC. Combinations that were included in United States Food and Drug Administration recommendations or European Association of Urology guidelines were used for analysis. We performed a meta-analysis with a random effects model to evaluate the efficacy of immunotherapy-VEGFR inhibitor combinations compared with sunitinib in favorable risk and elderly patients.
Our analysis demonstrated that progression-free survival (PFS) was significantly prolonged with combination therapy compared with sunitinib in patients with age > 65 years (hazard ratio, 0.66; 95% confidence interval, 0.52-0.84; P = .001). The PFS in favorable risk disease was improved with combination therapy compared with sunitinib, but the difference was not statistically significant (hazard ratio, 0.68; 95% confidence interval, 0.46-1.01; P = .055).
Our meta-analysis strengthens the trend of beneficial effect in prolonging PFS in both subgroups compared with each trial alone, indicating that favorable risk and elderly patients with mRCC likely benefit from combining programmed cell death 1 or programmed cell death-ligand 1 and VEGFR inhibition.
免疫检查点抑制剂和血管内皮生长因子受体（VEGFR）酪氨酸激酶抑制剂是转移性肾细胞癌（mRCC）最常用的药物。最近，大型临床试验表明，与单独使用 VEGFR 抑制剂相比，联合使用免疫检查点加 VEGFR 抑制的患者有更好的结果。然而，在有利风险（基于国际转移性肾细胞癌数据库联盟评分）和老年（年龄>65 岁）患者中的获益并不明确，这导致了美国食品和药物管理局与欧洲泌尿外科学会建议之间的差异。
我们搜索了可用于评估未经治疗的 mRCC 患者中免疫治疗联合 VEGFR 抑制剂与标准治疗相比的疗效的 III 期随机临床试验的相关文献。我们使用了被美国食品和药物管理局建议或欧洲泌尿外科学会指南纳入的联合方案进行分析。我们使用随机效应模型进行荟萃分析，以评估免疫治疗-VEGFR 抑制剂联合方案与舒尼替尼相比在有利风险和老年患者中的疗效。
我们的分析表明，与舒尼替尼相比，联合治疗在年龄>65 岁的患者中显著延长了无进展生存期（PFS）（风险比，0.66；95%置信区间，0.52-0.84；P=0.001）。在有利风险疾病中，联合治疗与舒尼替尼相比改善了 PFS，但差异无统计学意义（风险比，0.68；95%置信区间，0.46-1.01；P=0.055）。
我们的荟萃分析加强了与每个试验单独相比，在两个亚组中延长 PFS 的有益效果趋势，这表明有利风险和老年 mRCC 患者可能受益于联合使用程序性细胞死亡 1 或程序性细胞死亡配体 1 和 VEGFR 抑制。
