Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: final analysis of efficacy and safety from the phase III CheckMate 214 trial.

We report final efficacy and safety results with 9.3 years median follow-up.

我们报告了9.3年的中位随访时间的最终疗效和安全性结果。

patients_and_methods

Patients (N = 1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks × four doses, followed by NIVO (3 mg/kg or 240 mg every 2 weeks or 480 mg every 4 weeks); or sunitinib (SUN) (50 mg) once daily (4 weeks on, 2 weeks off).

患者（N = 1096）被随机分配接受NIVO 3 mg/kg联合IPI 1 mg/kg，每3周一次，共四次剂量，随后是NIVO（3 mg/kg或240 mg每两周一次或480 mg每四周一次）；或SUN（50 mg）每日一次（4周服用，2周停药）。

endpoints

overall survival(OS), and independent radiology review committee-assessed progression-free survivaland objective response ratein International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk (primary), intention-to-treat(secondary), and IMDC favorable-risk (exploratory) patients.

总体生存（OS），以及独立放射学审查委员会评估的无进展生存期和客观缓解率在国际转移性肾细胞癌数据库联盟（IMDC）中等/差风险（主要终点）、意向治疗（次要终点）和IMDC良好风险（探索性）患者中进行评估。

Results

With a median (range) follow-up of 9.3 years (8.6-9.9 years), the hazard ratio(95% confidence interval) for OS with NIVO + IPI versus SUN was 0.71 (0.62-0.82) in intention-to-treatpatients, 0.69 (0.59-0.81) in intermediate/poor-risk patients, and 0.80 (0.59-1.09) in favorable-risk patients; 108-month OS probabilities were 31.4% versus 19.5%, 30.2% versus 18.7%, and 35.3% versus 21.8%, respectively.

在中位随访时间为9.3年（范围8.6-9.9年）的情况下，NIVO + IPI与SUN治疗方案的总生存（OS）风险比（95%置信区间）在意向治疗患者中为0.71（0.62-0.82），在中危/差危患者中为0.69（0.59-0.81），在良好风险患者中为0.80（0.59-1.09）；108个月的OS概率分别为31.4%对比19.5%，30.2%对比18.7%，以及35.3%对比21.8%。

Progression-free survivalprobabilities at 96 months were 22.7% versus 9.0% (intention-to-treat), 25.4% versus 8.5% (intermediate/poor risk), and 12.5% versus 11.3% (favorable risk).

96个月无进展生存（PFS）概率分别为22.7%对比9.0%（意向治疗），25.4%对比8.5%（中危/差危），以及12.5%对比11.3%（良好风险）。

Probabilities of remaining in response at 96 months with NIVO + IPI versus SUN were 48.0% versus 19.0% (intention-to-treat), 50.0% versus 23.0% (intermediate/poor risk), and 36.0% versus not estimable (favorable risk).

在96个月时，NIVO + IPI组与SUN组维持反应的概率分别为48.0%对19.0%（意向治疗人群），50.0%对23.0%（中危/高危风险），以及36.0%对无法估计（低危风险）。

Incidenceof any-grade (grade 3-4) treatment-related adverse events (AEs) was 94.1% (48.6%) with NIVO + IPI versus 97.6% (64.1%) with SUN.

NIVO + IPI组与SUN组的任何级别（3-4级）治疗相关不良事件（AEs）的发生率分别为94.1%（48.6%）与97.6%（64.1%）。

Exploratory post hoc analyses reported include descriptive analyses of OS by immune-mediated AE discontinuation status.

报告的探索性事后分析包括按免疫介导的不良事件（AE）停药状态描述的总生存（OS）分析。

Conclusions

In the longest phase III follow-up of a first-line checkpoint inhibitor combination in aRCC (>9 years), NIVO + IPI maintained a substantial survival benefit with durable responses versus SUN.

在晚期肾细胞癌（aRCC）一线检查点抑制剂联合治疗的最长的III期随访中（>9年），纳武单抗（NIVO）加伊匹木单抗（IPI）与舒尼替尼（SUN）相比，维持了显著的生存益处和持久的反应。

Grade 3-4 treatment-related AEs were lower with NIVO + IPI versus SUN at 9 years.

与 SUN 相比，NIVO + IPI 在 9 年时 3-4 级治疗相关不良事件的发生率较低。

NIVO + IPI remains a first-line standard of care in aRCC.

NIVO + IPI 仍然是晚期肾细胞癌（aRCC）一线治疗的标准护理。