FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma
| Autor: | Mark Paciga, Emmanuel Sampene, Jingyu Yu, Patricia Keegan, Rashmi Rawat, Hong Zhao, Jennie T. Chang, Hongshan Li, Deborah Schmiel, Runyan Jin, Richard Pazdur, Whitney S. Helms, Marc R. Theoret, Kun He, Shawna L. Weis, Meredith K. Chuk, Liang Zhao |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf 0301 basic medicine Cancer Research medicine.medical_specialty Constipation Adolescent Drug-Related Side Effects and Adverse Reactions Hypophysitis Nausea Ipilimumab Pembrolizumab Antibodies Monoclonal Humanized Disease-Free Survival 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Drug Approval Melanoma Aged Pneumonitis Aged 80 and over Hepatitis business.industry Antibodies Monoclonal Middle Aged medicine.disease Rash Surgery 030104 developmental biology Oncology 030220 oncology & carcinogenesis Female medicine.symptom business medicine.drug |
| Zdroj: | Clinical Cancer Research. 23:5666-5670 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15–34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666–70. ©2017 AACR. |
| Databáze: | OpenAIRE |
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