Gustave Roussy, Villejuif, France.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Eur Urol. 2020 Apr;77(4):449-453. doi: 10.1016/j.eururo.2019.10.025. Epub 2019 Nov 13.
In the randomized, open-label, phase 3 CheckMate 214 trial, nivolumab plus ipilimumab (nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 wk for four doses, then nivolumab 3 mg/kg every 2 wk) had superior efficacy over sunitinib (50 mg once daily, 4 wk on, 2 wk off) in patients with untreated International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate- or poor-risk advanced renal cell carcinoma; the benefits were sustained through extended follow-up. To better characterize the association between outcomes and IMDC risk in CheckMate 214, we completed a post hoc analysis (n = 1051) of efficacy by the number of IMDC risk factors. The investigator-assessed objective response rate (ORR), overall survival (OS), and investigator-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors v1.1 were evaluated. ORR with nivolumab plus ipilimumab was consistent across zero to six IMDC risk factors, whereas with sunitinib it decreased with increasing number of risk factors. Benefits of nivolumab plus ipilimumab over sunitinib in terms of ORR (40-44% vs 16-38%), OS (hazard ratio [HR] 0.50-0.72), and PFS (HR 0.44-0.86) were consistently observed in subgroups with one, two, three, or four to six IMDC risk factors (p < 0.05 for treatment × no. of risk factors interaction). These results demonstrate the benefit of first-line nivolumab plus ipilimumab over sunitinib across all intermediate-risk and poor-risk groups, regardless of the number of IMDC risk factors. PATIENT SUMMARY: This report from the CheckMate 214 study describes a consistent efficacy benefit with first-line nivolumab plus ipilimumab over first-line sunitinib in all groups of patients with intermediate-risk or poor-risk advanced renal cell carcinoma, regardless of the number of risk factors they had before starting treatment. We conclude that there is a benefit of first-line treatment with nivolumab plus ipilimumab for all intermediate-risk patients, including those with one or two risk factors, and for all poor-risk patients, independent of the number of risk factors.
在随机、开放标签、III 期 CheckMate 214 试验中，纳武单抗联合伊匹单抗（纳武单抗 3mg/kg 联合伊匹单抗 1mg/kg，每 3 周一次，共 4 次，然后纳武单抗 3mg/kg，每 2 周一次）在未经治疗的国际转移性肾细胞癌数据库联盟（IMDC）中危或高危晚期肾细胞癌患者中的疗效优于舒尼替尼（50mg 每日一次，4 周治疗，2 周停药）；通过延长随访时间，这些益处得以维持。为了更好地描述 CheckMate 214 中结局与 IMDC 风险之间的关联，我们对疗效进行了事后分析（n=1051），根据 IMDC 风险因素的数量进行了评估。研究者评估的客观缓解率（ORR）、总生存期（OS）和研究者评估的无进展生存期（PFS）根据实体瘤反应评价标准 1.1 进行评估。纳武单抗联合伊匹单抗的 ORR 与零至六个 IMDC 风险因素一致，而舒尼替尼的 ORR 随着风险因素的增加而降低。纳武单抗联合伊匹单抗与舒尼替尼相比，ORR（40-44%比 16-38%）、OS（风险比 [HR]0.50-0.72）和 PFS（HR 0.44-0.86）的获益在具有一个、两个、三个或四个至六个 IMDC 风险因素的亚组中一致观察到（治疗与风险因素数量的交互作用 P<0.05）。这些结果表明，一线纳武单抗联合伊匹单抗在所有中危和高危组中均优于一线舒尼替尼，无论患者的 IMDC 风险因素数量如何。患者概要：来自 CheckMate 214 研究的这份报告描述了一线纳武单抗联合伊匹单抗在所有中危或高危晚期肾细胞癌患者中均优于一线舒尼替尼的一致疗效获益，无论他们在开始治疗前有多少个风险因素。我们的结论是，一线治疗用纳武单抗联合伊匹单抗对所有中危患者（包括有一个或两个风险因素的患者）和所有高危患者均有益，而与风险因素的数量无关。
