FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma

被引：64

作者：

Barone, Amy ^{[1
]}

Hazarika, Maitreyee ^{[1
]}

Theoret, Marc R. ^{[1
]}

Mishra-Kalyani, Pallavi ^{[2
]}

Chen, Huanyu ^{[2
]}

He, Kun ^{[2
]}

Sridhara, Rajeshwari ^{[2
]}

Subramaniam, Sriram ^{[3
]}

Pfuma, Elimika ^{[3
]}

Wang, Yaning ^{[3
]}

Li, Hongshan ^{[3
]}

Zhao, Hong ^{[3
]}

Zirkelbach, Jeanne Fourie ^{[3
]}

Keegan, Patricia ^{[1
]}

Pazdur, Richard ^{[1
]}

机构：

[1] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA

[2] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA

[3] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA

来源：

CLINICAL CANCER RESEARCH | 2017年 / 23卷 / 19期

关键词：

RESPONSE CRITERIA;

D O I：

10.1158/1078-0432.CCR-16-0664

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

On December 18, 2015, the FDA granted regular approval to pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma based on results of two randomized, open-label, active-controlled clinical trials. In trial PN006, 834 patients with ipilimumab-naive metastatic melanoma were randomized (1: 1: 1) to pembrolizumab 10 mg/kg i.v. every 2 or 3 weeks until disease progression or ipilimumab 3 mg/kg every 3 weeks for up to four doses. In trial PN002, 540 patients with ipilimumab-refractory metastatic melanoma were randomized (1:1:1) to pembrolizumab 2 or 10 mg/kg i.v. every 3 weeks or to investigator's choice of chemotherapy. In trial PN006, patients randomized to pembrolizumab demonstrated a statistically significant improvement in overall survival compared with ipilimumab [every-2-week arm: hazard ratio (HR) -0.63; 95% confidence interval (CI), 0.47-0.83; P < 0.001; every-3-week arm: HR = 0.69; 95% CI, 0.52-0.90; P = 0.004]. In both trials, patients receiving pembrolizumab demonstrated statistically significant improvements in progression-free survival. The most common (> 2%) immune-mediated adverse reactions in a pooled safety analysis were hypothyroidism, pneumonitis, and hyperthyroidism. Key considerations for approval were determination of pembrolizumab dose and interpretation of tumor response-based endpoints using RECIST or immune-related RECIST. (C) 2017 AACR.

引用

页码：5661 / 5665

页数：5