Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A).
Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A).
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DOI：
10.1200/jco.21.02938
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发表时间：
2022-09-01
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确定肿瘤细胞程序性死亡配体1（PD-L1）表达作为nivolumab单药治疗在未接受过治疗的透明细胞肾细胞癌（ccRCC）患者中疗效的预测生物标志物的价值，以及补救性nivolumab/ipilimumab在nivolumab单药治疗无反应的肿瘤患者中的疗效。符合条件的初治ccRCC患者接受纳武单抗治疗，直至疾病进展（PD）、毒性或完成96周治疗（A部分）。之前PD或48周时疾病稳定的患者可接受补救性纳武单抗/易普利姆玛（B部分）。主要终点是肿瘤PD-L1表达> 20%与0%患者的1年无进展生存期改善。123例患者入组。客观缓解率（ORR）为34.1%（95% CI，25.8 - 43.2）。国际转移性RCC数据库联盟分类的ORR为可危57.1%，中危/低危25.0%，肉瘤样特征为36.4%。肿瘤PD-L1表达为0、1-20或> 20%的患者的ORR分别为26.9%、50.0%和75.0%（趋势检验P值= 0.002）。中位缓解持续时间为27.6（19.3至未达到）个月，42例缓解者中有26例（包括20例可缓解风险疾病中的17例）保持无进展。PD-L1 = 0%和> 20%类别的1年无进展生存率分别为34.6%和75.0%（P = .050）。97例PD或疾病长期稳定患者可能有资格参加B部分，35例入组。部分B的ORR为11.4%。≥ 3级治疗相关不良事件发生在35%的nivolumab患者和43%的补救nivolumab/ipilimumab患者中。纳武单抗单药治疗在初治ccRCC中具有活性。尽管在中危/低危患者中的疗效似乎低于nivolumab/ipilimumab，但低危患者有显著的获益。疗效与肿瘤PD-L1状态相关。补救性nivolumab/ipilimumab通常不可行，且获益有限。
To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive to nivolumab monotherapy. Eligible patients with treatment-naive ccRCC received nivolumab until progressive disease (PD), toxicity, or completing 96 treatment weeks (part A). Patients with PD before or stable disease at 48 weeks could receive salvage nivolumab/ipilimumab (part B). The primary end point was improvement in 1-year progression-free survival in patients with tumor PD-L1 expression > 20% versus 0%. One hundred twenty-three patients were enrolled. The objective response rate (ORR) was 34.1% (95% CI, 25.8 to 43.2). ORR by International Metastatic RCC Database Consortium category was favorable-risk 57.1%, intermediate-risk/poor-risk 25.0%, and by sarcomatoid features 36.4%. The ORR was 26.9%, 50.0%, and 75.0% for patients with the tumor PD-L1 expression of 0, 1-20, or > 20%, respectively (trend test P value = .002). The median duration of response was 27.6 (19.3 to not reached) months, with 26 of 42 responders including 17 of 20 with favorable-risk disease remaining progression-free. The 1-year progression-free survival was 34.6% and 75.0% in the PD-L1 = 0% and > 20% categories, respectively (P = .050). Ninety-seven patients with PD or prolonged stable disease were potentially eligible for part B, and 35 were enrolled. The ORR for part B was 11.4%. Grade ≥ 3 treatment-related adverse events occurred in 35% of patients on nivolumab and 43% of those on salvage nivolumab/ipilimumab. Nivolumab monotherapy is active in treatment-naive ccRCC. Although efficacy appears to be less than that of nivolumab/ipilimumab in patients with intermediate-risk/poor-risk disease, favorable-risk patients had notable benefit. Efficacy correlated with tumor PD-L1 status. Salvage nivolumab/ipilimumab was frequently not feasible and of limited benefit.