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☆

IF 80.4 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2026-07-01 Epub Date: 2026-03-03 DOI:10.1016/j.annonc.2026.02.017

T.K. Choueiri, L. Albigès, D.F. McDermott, H.J. Hammers, B. Escudier, M. Burotto, E.R. Plimack, C. Porta, S. George, T. Powles, F. Donskov, M.B. Atkins, H. Gurney, C.K. Kollmannsberger, M.-O. Grimm, C. Barrios, D. Castellano, V. Grünwald, Y. Tomita, B.I. Rini, R.J. Motzer

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引用次数: 0

Abstract

Background

Nivolumab plus ipilimumab (NIVO + IPI) demonstrated significant long-term survival and response benefits in patients with previously untreated advanced renal cell carcinoma (aRCC) in the phase III CheckMate 214 trial (NCT02231749). We report final efficacy and safety results with 9.3 years median follow-up.

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

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-treat patients, 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. Progression-free survival probabilities 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). 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). Incidence of 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. Exploratory post hoc analyses reported include descriptive analyses of OS by immune-mediated AE discontinuation status.

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. Grade 3-4 treatment-related AEs were lower with NIVO + IPI versus SUN at 9 years. NIVO + IPI remains a first-line standard of care in aRCC.

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Nivolumab联合ipilimumab对抗舒尼替尼一线治疗晚期肾细胞癌：来自CheckMate 214 III期试验的有效性和安全性的最终分析

背景：在CheckMate 214 III期试验（NCT02231749）中，Nivolumab + ipilimumab （NIVO+IPI）在先前未经治疗的晚期肾细胞癌（aRCC）患者中显示出显着的长期生存和应答益处。我们报告了中位随访9.3年的最终疗效和安全性结果。患者和方法：患者（N=1096）随机接受NIVO 3mg /kg + IPI 1mg /kg Q3W × 4个剂量，其次是NIVO (3mg /kg或240 mg Q2W或480 mg Q4W)；或舒尼替尼（SUN）（50mg） QD（服用4周，停用2周）。终点：IMDC中/低风险（原发性）、意向治疗（继发性）和有利风险（探索性）患者的总生存期（OS）和独立放射学审查委员会评估的无进展生存期（PFS）和客观缓解率（ORR）。结果：中位（范围）随访时间为9.3（8.6-9.9）年，NIVO+IPI OS与SUN的风险比（HR； 95%可信区间[CI]）在意向治疗患者中为0.71(0.62-0.82)，在中/低风险患者中为0.69(0.59-0.81)，在有利风险患者中为0.80 (0.59-1.09)；108个月OS概率分别为31.4%对19.5%，30.2%对18.7%，35.3%对21.8%。96个月时PFS概率分别为22.7%对9.0%（意向治疗），25.4%对8.5%（中/低风险），12.5%对11.3%（有利风险）。NIVO+IPI与SUN在96个月时保持缓解的概率分别为48.0%对19.0%（意向治疗），50.0%对23.0%（中/低风险），36.0%对不可估计（有利风险）。NIVO+IPI组任何级别（3-4级）治疗相关不良事件（ae）的发生率为94.1%(48.6%)，而SUN组为97.6%（64.1%）。探索性事后分析报告包括免疫介导的AE停止状态对OS的描述性分析。结论：在一线检查点抑制剂联合治疗aRCC的最长III期随访中（bbbb9年），NIVO+IPI与SUN相比，具有持久的生存获益。9年时，NIVO+IPI组与SUN组相比，3-4级治疗相关ae较低。NIVO+IPI仍然是aRCC的一线治疗标准。

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.