皮下注射与静脉注射纳武单抗治疗肾细胞癌的比较。

Subcutaneous versus intravenous nivolumab for renal cell carcinoma.

作者信息

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

机构信息

Department of Oncology, Institut Gustave Roussy, Villejuif, France.

Urologic Oncology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

出版信息

Ann Oncol. 2025 Jan;36(1):99-107. doi: 10.1016/j.annonc.2024.09.002. Epub 2024 Sep 15.

DOI:10.1016/j.annonc.2024.09.002

PMID:39288844

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), and minimum steady-state serum concentration (C); 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 and C 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.

摘要

背景

不断演变的肿瘤治疗模式对改善患者体验和医疗保健效率的给药方式产生了未满足的需求。

患者与方法

CheckMate 67T（NCT04810078）是一项III期、开放标签、多中心、非劣效性试验，其中晚期/转移性透明细胞肾细胞癌患者被随机分为皮下注射纳武利尤单抗（每4周1200mg；与重组人透明质酸酶PH20 20000单位共同配制）或静脉注射纳武利尤单抗（每2周3mg/kg）。主要目标是通过根据群体药代动力学分析确定的共同主要终点评估皮下注射与静脉注射纳武利尤单抗的非劣效性[前28天的时间平均血清浓度（C）和最低稳态血清浓度（C）；非劣效性阈值：几何平均比值（GMR）的90%置信区间（CI）的下限≥0.8]。客观缓解率（ORR）是一个关键的次要终点，具有非劣效性效力[非劣效性阈值：ORR（皮下注射与静脉注射纳武利尤单抗）相对风险的95%CI的下限≥0.60]。

结果

总体而言，495例患者被随机分组。皮下注射组与静脉注射组中C和C的GMR报告的相对暴露量分别为2.098（90%CI 2.001 - 2.200）和1.774（90%CI 1.633 - 1.927）。在最短随访8个月后，皮下注射纳武利尤单抗的ORR为24.2%（95%CI 19.0% - 30.0%），而静脉注射纳武利尤单抗的ORR为18.2%[95%CI 13.6% - 23.6%；相对风险：1.33（95%CI 0.94 - 1.87）]。共同主要终点和ORR均达到非劣效性阈值。其他疗效和安全性指标相似。