Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma.
Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma.
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DOI：
10.1200/jco.20.02365
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发表时间：
2021-03-20
期刊：
影响因子：
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通讯作者：
Atkins MB
中科院分区：
文献类型：
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作者：
McDermott DF;Lee JL;Ziobro M;Suarez C;Langiewicz P;Matveev VB;Wiechno P;Gafanov RA;Tomczak P;Pouliot F;Donskov F;Alekseev BY;Shin SJ;Bjarnason GA;Castellano D;Silverman RK;Perini RF;Schloss C;Atkins MB
尚未在非透明细胞肾细胞癌（nccRCC）患者中前瞻性评价程序性死亡1（PD-1）通路抑制剂。II期KEYNOTE-427研究（队列B）旨在评估PD-1抑制剂派姆单抗单药治疗晚期nccRCC的疗效和安全性。经组织学证实、可测量（实体瘤疗效评价标准[RECIST]第1.1版）nccRCC且既往未接受全身治疗的患者接受帕博利珠单抗200 mg静脉给药，每3周一次，持续≤ 24个月。主要终点是根据RECIST v1.1的客观缓解率（ORR）。在入组的患者（N = 165）中，71.5%的患者确诊为乳头状，12.7%的患者为嫌色细胞，15.8%的患者为未分类的RCC组织学。大多数患者（67.9%）的国际转移性RCC数据库联盟风险状态为中等或较差，肿瘤程序性死亡配体1（PD-L1）联合阳性评分（CPS）≥ 1（61.8%）。从入组至数据库截止日期的中位时间为31.5个月（范围：22.7-38.8）。所有患者的ORR为26.7%。中位缓解持续时间为29.0个月; 59.7%的缓解持续时间≥ 12个月。CPS ≥ 1和CPS < 1状态的ORR分别为35.3%和12.1%。根据组织学分类，乳头状、嫌色和未分类的ORR分别为28.8%、9.5%和30.8%。总体而言，中位无进展生存期为4.2个月（95% CI，2.9 - 5.6）; 24个月率为18.6%。中位总生存期为28.9个月（95% CI，24.3个月至未达到）; 24个月率为58.4%。总体而言，69.7%的患者报告了治疗相关不良事件，最常见的是瘙痒症（20.0%）和甲状腺功能减退症（14.5%）。2例死亡与治疗相关（肺炎和心脏骤停）。一线pembrolizumab单药治疗在nccRCC中显示出有希望的抗肿瘤活性。安全性特征与在其他肿瘤类型中观察到的相似。
Programmed death 1 (PD-1) pathway inhibitors have not been prospectively evaluated in patients with non–clear cell renal cell carcinoma (nccRCC). The phase II KEYNOTE-427 study (cohort B) was conducted to assess the efficacy and safety of single-agent pembrolizumab, a PD-1 inhibitor, in advanced nccRCC. Patients with histologically confirmed, measurable (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) nccRCC and no prior systemic therapy received pembrolizumab 200 mg intravenously once every 3 weeks for ≤ 24 months. The primary end point was objective response rate (ORR) per RECIST v1.1. Among enrolled patients (N = 165), 71.5% had confirmed papillary, 12.7% had chromophobe, and 15.8% had unclassified RCC histology. Most patients (67.9%) had intermediate or poor International Metastatic RCC Database Consortium risk status and tumors with programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 1 (61.8%). The median time from enrollment to database cutoff was 31.5 months (range, 22.7-38.8). In all patients, the ORR was 26.7%. The median duration of response was 29.0 months; 59.7% of responses lasted ≥ 12 months. The ORR by CPS ≥ 1 and CPS < 1 status was 35.3% and 12.1%, respectively. The ORR by histology was 28.8% for papillary, 9.5% for chromophobe, and 30.8% for unclassified. Overall, the median progression-free survival was 4.2 months (95% CI, 2.9 to 5.6); the 24-month rate was 18.6%. The median overall survival was 28.9 months (95% CI, 24.3 months to not reached); the 24-month rate was 58.4%. Overall, 69.7% of patients reported treatment-related adverse events, most commonly pruritus (20.0%) and hypothyroidism (14.5%). Two deaths were treatment related (pneumonitis and cardiac arrest). First-line pembrolizumab monotherapy showed promising antitumor activity in nccRCC. The safety profile was similar to that observed in other tumor types.