Subcutaneous versus intravenous nivolumab for renal cell carcinoma☆

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-01-01 DOI:10.1016/j.annonc.2024.09.002

L. Albiges , M.T. Bourlon , M. Chacón , H.J. Cutuli , Y.A.L. Chuken , B. Żurawski , J.M. Mota , I. Magri , M. Burotto , M. Luz , J. de Menezes , E.P.Y. Ruiz , S. Fu , M. Richardet , B.P. Valderrama , M. Maruzzo , S. Bracarda , M. Breckenridge , H.E. Vezina , D. Rathod , S. George

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引用次数: 0

Abstract

Background

The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and health care efficiencies.

Patients and methods

CheckMate 67T (NCT04810078) was a phase III, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20 000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). The primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis [time-averaged serum concentration over the first 28 days (C_avgd28), and minimum steady-state serum concentration (C_minss); noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios (GMR) ≥0.8]. Objective response rate (ORR) was a key secondary endpoint powered for noninferiority [noninferiority threshold: lower boundary of 95% CI of relative risk of ORR (subcutaneous versus intravenous nivolumab) ≥0.60].

Results

Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of C_avgd28 and C_minss was 2.098 (90% CI 2.001-2.200) and 1.774 (90% CI 1.633-1.927), respectively. After 8 months of minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI 19.0%-30.0%) versus 18.2% with intravenous nivolumab [95% CI 13.6%-23.6%; relative risk: 1.33 (95% CI 0.94-1.87)]. Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar.

Conclusions

Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed.

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皮下注射与静脉注射尼妥珠单抗治疗肾细胞癌。

背景不断发展的肿瘤治疗模式产生了对能改善患者体验和提高医疗效率的给药方案的未满足需求。患者和方法CheckMate 67T（NCT04810078）是一项3期、开放标签、多中心、非劣效性试验，在这项试验中，晚期/转移性透明细胞肾细胞癌患者被随机分配到皮下注射尼妥珠单抗（1200 毫克，每4 周一次；与重组人透明质酸酶 PH20 20,000 单位共同配制）或静脉注射尼妥珠单抗（3 毫克/千克，每2 周一次）。主要目的是通过群体药代动力学分析（前28天的时间平均血清浓度[Cavgd28]和最低稳态血清浓度[Cminss]；非劣效阈值：几何平均比[GMR]≥0.8的90%置信区间(CI)的下界）确定的共侧终点，评估皮下注射与静脉注射尼妥珠单抗的非劣效性。客观反应率（ORR）是非劣效性的关键次要终点（非劣效阈值：ORR相对风险[皮下注射与静脉注射尼妥珠单抗]的95%置信区间下限≥0.60）。根据Cavgd28和Cminss的GMR报告，皮下注射组与静脉注射组的相对暴露分别为2.098（90% CI，2.001-2.200）和1.774（90% CI，1.633-1.927）。经过至少8个月的随访，皮下注射尼妥珠单抗的ORR为24.2%（95% CI，19.0-30.0），而静脉注射尼妥珠单抗的ORR为18.2%（95% CI，13.6-23.6；相对风险：1.33 [95% CI，0.94-1.87]）。主要终点和ORR达到了非劣效性阈值。结论根据药代动力学和ORR，皮下注射尼妥珠单抗的疗效不劣于静脉注射尼妥珠单抗。未观察到新的安全性信号。

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.