Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915).
Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915).
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DOI：
10.1200/jco.22.00533
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发表时间：
2023-01-20
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Ipilimumab和nivolumab各自显示出对高风险切除的黑色素瘤的治疗益处。III期CheckMate 915试验在切除的IIIB-D或IV期黑色素瘤患者中评估了辅助nivolumab + ipilimumab与单独nivolumab。在这项随机、双盲、III期试验中，1，833例患者接受nivolumab 240 mg每2周一次+ipilimumab 1 mg/kg每6周一次（916例患者）或nivolumab 480 mg每4周一次（917例患者）≤ 1年。随机分配后，患者按肿瘤程序性死亡配体1（PD-L1）表达和分期分层。双重主要终点是随机分配的患者和肿瘤PD-L1表达水平< 1%亚组的无复发生存期（RFS）。在至少约23.7个月的随访中，在全随机分配的患者人群（风险比，0.92; 95% CI，0.77至1.09; P = 0.269）或PD-L1表达< 1%的患者（风险比，0.91; 95% CI，0.73至1.14）中，治疗组之间的RFS无显著差异。在所有患者中，24个月RFS率分别为64.6%（联合治疗）和63.2%（纳武单抗）。联合治疗组中32.6%的患者和纳武利尤单抗组中12.8%的患者报告了治疗相关的3级或4级不良事件。联合治疗组有0.4%的患者报告了治疗相关死亡，nivolumab治疗组无患者报告。在IIIB-D期或IV期黑色素瘤患者中，与纳武单抗480 mg每4周一次相比，纳武单抗240 mg每2周一次加伊匹单抗1 mg/kg每6周一次未改善RFS。纳武单抗显示出与先前在类似于使用美国癌症联合委员会第八版的当前实践的人群中进行的辅助研究一致的疗效，重申纳武单抗作为黑色素瘤辅助治疗的标准护理。
Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma. In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup. At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients. Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.