纳武利尤单抗联合伊匹单抗对比舒尼替尼用于晚期肉瘤样肾细胞癌患者一线治疗的疗效和安全性。
Efficacy and Safety of Nivolumab Plus Ipilimumab versus Sunitinib in First-line Treatment of Patients with Advanced Sarcomatoid Renal Cell Carcinoma.
机构信息
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
出版信息
Clin Cancer Res. 2021 Jan 1;27(1):78-86. doi: 10.1158/1078-0432.CCR-20-2063. Epub 2020 Sep 1.
PURPOSE
Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognoses and suboptimal outcomes with targeted therapy. This analysis of the phase III CheckMate 214 trial analyzed the efficacy of nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in patients with sRCC.
PATIENTS AND METHODS
Patients with sRCC were identified via independent central pathology review of archival tumor tissue or histologic classification per local pathology report. Patients were randomized 1:1 to receive nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks (four doses) then nivolumab 3 mg/kg every 2 weeks, or sunitinib 50 mg orally every day (4 weeks; 6-week cycles). Outcomes in patients with sRCC were not prespecified. Endpoints in patients with sRCC and International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk disease included overall survival (OS), progression-free survival (PFS) per independent radiology review, and objective response rate (ORR) per RECIST v1.1. Safety outcomes used descriptive statistics.
RESULTS
Of 1,096 randomized patients in CheckMate 214, 139 patients with sRCC and intermediate/poor-risk disease and six with favorable-risk disease were identified. With 42 months' minimum follow-up in patients with sRCC and intermediate/poor-risk disease, median OS [95% confidence interval (CI)] favored NIVO+IPI [not reached (NR) (25.2-not estimable [NE]); = 74] versus sunitinib [14.2 months (9.3-22.9); = 65; HR, 0.45 (95% CI, 0.3-0.7; = 0.0004)]; PFS benefits with NIVO+IPI were similarly observed [median 26.5 vs. 5.1 months; HR, 0.54 (95% CI, 0.33-0.86; = 0.0093)]. Confirmed ORR was 60.8% with NIVO+IPI versus 23.1% with sunitinib, with complete response rates of 18.9% versus 3.1%, respectively. No new safety signals emerged.
CONCLUSIONS
NIVO+IPI showed unprecedented long-term survival, response, and complete response benefits versus sunitinib in previously untreated patients with sRCC and intermediate/poor-risk disease, supporting the use of first-line NIVO+IPI for this population..
目的
具有肉瘤样特征的晚期肾细胞癌（sRCC）患者采用靶向治疗预后较差，结局不佳。这项 III 期 CheckMate 214 试验分析了纳武利尤单抗联合伊匹单抗（NIVO+IPI）与舒尼替尼治疗 sRCC 患者的疗效。
方法
通过对存档肿瘤组织进行独立中心病理复查或根据当地病理报告进行组织学分类，鉴定 sRCC 患者。患者按 1:1 比例随机分配，接受纳武利尤单抗（3 mg/kg）联合伊匹单抗（1 mg/kg）每 3 周（4 个剂量），然后每 2 周接受纳武利尤单抗 3 mg/kg，或舒尼替尼 50 mg 每日口服（4 周；6 周周期）。sRCC 患者的结局未预先设定。sRCC 患者和国际转移性肾细胞癌数据库联盟中中/高危疾病患者的结局包括总生存期（OS）、独立影像学评估的无进展生存期（PFS）和按 RECIST v1.1 评估的客观缓解率（ORR）。安全性结局采用描述性统计方法。
结果
在 CheckMate 214 中随机分配的 1096 例患者中，鉴定出 139 例 sRCC 患者伴中/高危疾病和 6 例伴低危疾病。在 sRCC 和中/高危疾病患者中，中位随访时间至少为 42 个月，OS （95%CI）倾向于 NIVO+IPI [未达到（NR）（25.2-无法评估[NE]）； = 74]，而非舒尼替尼 [14.2 个月（9.3-22.9）； = 65；HR，0.45（95%CI，0.3-0.7； = 0.0004)]；NIVO+IPI 也观察到 PFS 获益 [中位 26.5 与 5.1 个月；HR，0.54（95%CI，0.33-0.86； = 0.0093)]。NIVO+IPI 的确认 ORR 为 60.8%，而舒尼替尼为 23.1%，完全缓解率分别为 18.9%和 3.1%。未出现新的安全性信号。
结论
在未接受治疗的 sRCC 伴中/高危疾病患者中，与舒尼替尼相比，NIVO+IPI 显示出前所未有的长期生存、应答和完全缓解获益，支持将一线治疗方案用于该人群。
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