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

Abstract

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-naïve 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. Clin Cancer Res; 23(19); 5661-5. ©2017 AACR.

• Authors: Amy Barone, Maitreyee Hazarika, Marc R Theoret, Pallavi Mishra-Kalyani, Huanyu Chen, Kun He, Rajeshwari Sridhara, Sriram Subramaniam, Elimika Pfuma, Yaning Wang, Hongshan Li, Hong Zhao, Jeanne Fourie Zirkelbach, Patricia Keegan, Richard Pazdur
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 19 Pg. 5661-5665 (Oct 01 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28179454 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Ipilimumab
• pembrolizumab

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug Approval
• Drug-Related Side Effects and Adverse Reactions (pathology)
• Female
• Humans
• Ipilimumab (administration & dosage, adverse effects)
• Male
• Melanoma (drug therapy, pathology, surgery)
• Middle Aged