Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial.

We report final, updated efficacy and safety results with median follow-up of 5.6 years.

我们报告了中位随访5.6年后的最终、更新的疗效和安全性结果。

patients_and_methods

Patients with advanced RCC were randomized to first-line NIVO 240 mg intravenously every 2 weeks plus CABO 40 mg p.o. o.d. or SUN 50 mg p.o. o.d.

晚期肾细胞癌患者被随机分配接受一线NIVO 240 mg静脉注射每两周一次，联合CABO 40 mg口服每日一次或SUN 50 mg口服每日一次。

(4 weeks each 6-week cycle) until disease progression or unacceptable toxicity (maximum 2 years of NIVO).

(每6周为一个周期，每个周期4周)直至疾病进展或出现不可接受的毒性反应(最多接受NIVO治疗2年)。

The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR).

主要终点是根据盲法独立中央审查（BICR）按RECIST v1.1标准评估的无进展生存期（PFS）。

Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety.

次要终点包括总生存期（OS）、根据RECIST v1.1标准通过BICR评估的客观缓解率（ORR）以及安全性。

Results

Median (range) follow-up was 5.6 years [67.6 (60.2-80.2) months].

中位随访时间（范围）为5.6年[67.6 (60.2-80.2)个月]。

In intent-to-treat patients (NIVO+CABO, n = 323; SUN, n = 328), PFS favored NIVO+CABO versus SUN [hazard ratio(HR) 0.58, 95% confidence interval(CI) 0.49-0.70].

在意向治疗患者中（NIVO+CABO，n = 323；SUN，n = 328），无进展生存期（PFS）倾向于NIVO+CABO与SUN相比[风险比（HR）0.58，95%置信区间（CI）0.49-0.70]。

Median PFS was 16.4 versus 8.3 months, respectively; 60-month PFS rates were 13.6% versus 3.6%.

中位无进展生存期分别为16.4个月和8.3个月；60个月无进展生存率分别为13.6%和3.6%。

OS favored NIVO+CABO versus SUN (HR 0.79, 95% CI 0.65-0.96).

总生存期方面，NIVO+CABO组优于SUN组（风险比0.79，95%置信区间0.65-0.96）。

Median OS was 46.5 versus 35.5 months, respectively; 60-month OS rates were 40.9% versus 35.4%.

中位总生存期分别为46.5个月和35.5个月；60个月的总生存率分别为40.9%和35.4%。

ORR was greater with NIVO+CABO versus SUN (55.7% versus 27.4%; complete response 13.9% versus 4.6%).

与SUN相比，NIVO+CABO的客观缓解率更高（55.7%对比27.4%；完全缓解率为13.9%对比4.6%）。

The probability of remaining in response through 60 months with NIVO+CABO versus SUN was 22.0% versus 10.0%.

在接受NIVO+CABO治疗与SUN治疗的患者中，60个月内持续响应的概率分别为22.0%和10.0%。

In all treated patients (n = 320 each arm), any-grade (grade 3-4) treatment-related adverse events occurred in 97.5% (67.8%) versus 93.1% (55.0%) with NIVO+CABO versus SUN, respectively.

在每组320名接受治疗的患者中，NIVO+CABO与SUN治疗相关的任何级别的（3-4级）不良事件发生率分别为97.5%（67.8%）和93.1%（55.0%）。

No new deaths due to study drug toxicity occurred since the 32.9-month median follow-up.

自中位随访时间32.9个月以来，未发生因研究药物毒性导致的新死亡事件。

Conclusions

Long-term efficacy benefit was observed with NIVO+CABO over SUN in this final follow-up from CheckMate 9ER and safety was consistent with previous reports.

在CheckMate 9ER的最终随访中，观察到NIVO+CABO与SUN相比具有长期的疗效优势，安全性与以往报告一致。

These results reaffirm NIVO+CABO as a standard of care for previously untreated advanced RCC.

这些结果再次确认了NIVO+CABO作为先前未治疗的晚期肾细胞癌的标准治疗方法。