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

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-09-23 DOI:10.1016/j.annonc.2025.09.006

R J Motzer, B Escudier, M Burotto, T Powles, A B Apolo, M T Bourlon, A Y Shah, C Porta, C Suárez, C H Barrios, M Richardet, H Gurney, E R Kessler, Y Tomita, J Bedke, C Scheffold, M Askelson, J Panzica, J Zhang, M van Kooten Losio, T K Choueiri

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引用次数: 0

Abstract

Background: Nivolumab plus cabozantinib (NIVO+CABO) showed significant benefits over sunitinib (SUN) in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for previously untreated advanced renal cell carcinoma (RCC) in the phase III CheckMate 9ER trial. We report final, updated efficacy and safety results with median follow-up of 5.6 years.

Patients and methods: Patients with advanced RCC were randomized to first-line NIVO 240 mg IV every 2 weeks plus CABO 40 mg PO QD or SUN 50 mg PO QD (4 weeks each 6-week cycle) until disease progression or unacceptable toxicity (maximum 2 years of NIVO). The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety.

Results: Median (range) follow-up was 5.6 years (67.6 [60.2-80.2] months). In intent-to-treat patients (NIVO+CABO, n=323; SUN, n=328), PFS favored NIVO+CABO versus SUN (hazard ratio [HR], 0.58 [95% 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%. OS favored NIVO+CABO versus SUN (HR, 0.79 [95% CI, 0.65-0.96]). Median OS was 46.5 versus 35.5 months, respectively; 60-month OS rates were 40.9% versus 35.4%. ORR was greater with NIVO+CABO versus SUN (55.7% versus 27.4%; complete response, 13.9% versus 4.6%). The probability of remaining in response through 60 months with NIVO+CABO versus SUN was 22.0% versus 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. No new deaths due to study drug toxicity occurred since the 32.9-month median follow-up.

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

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纳武单抗联合卡博赞替尼治疗晚期肾细胞癌的最终分析来自随机III期CheckMate 9ER试验。

背景：在III期CheckMate 9ER试验中，尼沃单抗加卡博赞替尼（NIVO+CABO）在治疗先前未治疗的晚期肾细胞癌（RCC）的无进展生存期（PFS）、总生存期（OS）和客观缓解率（ORR）方面均优于舒尼替尼（SUN）。我们报告了最终的、最新的疗效和安全性结果，中位随访时间为5.6年。患者和方法：晚期RCC患者随机分配至一线NIVO 240 mg IV，每2周加CABO 40 mg PO QD或SUN 50 mg PO QD（每6周周期4周），直到疾病进展或不可接受的毒性（NIVO最长2年）。通过盲法独立中心评价（BICR），主要终点为RECIST v1.1标准的PFS。次要终点包括OS、BICR按RECIST v1.1计算的ORR和安全性。结果：中位（范围）随访为5.6年（67.6[60.2-80.2]个月）。在意向治疗患者（NIVO+CABO, n=323； SUN, n=328）中，PFS倾向于NIVO+CABO而不是SUN（风险比[HR]， 0.58 [95% CI, 0.49-0.70]）。中位PFS分别为16.4个月和8.3个月；60个月PFS率分别为13.6%和3.6%。OS倾向于NIVO+CABO与SUN （HR, 0.79 [95% CI, 0.65-0.96]）。中位OS分别为46.5个月和35.5个月；60个月的OS率分别为40.9%和35.4%。NIVO+CABO组的ORR高于SUN组（55.7%比27.4%；完全缓解，13.9%比4.6%）。与SUN相比，NIVO+CABO在60个月内保持缓解的概率分别为22.0%和10.0%。在所有接受治疗的患者中（每组320例），NIVO+CABO与SUN的任何级别（3-4级）治疗相关不良事件发生率分别为97.5%（67.8%）和93.1%（55.0%）。自32.9个月的中位随访以来，未发生新的研究药物毒性死亡。结论：在CheckMate 9ER的最后随访中，观察到NIVO+CABO优于SUN的长期疗效，安全性与先前的报道一致。这些结果重申了NIVO+CABO作为先前未治疗的晚期RCC的标准治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.