FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors.

Abstract

The FDA approved pembrolizumab on May 23, 2017, for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H), or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and for the treatment of unresectable or metastatic MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The FDA granted the approval based on an understanding of the biology of MSI-H/dMMR across different tumors along with the clinically important effects on overall response rate (ORR) observed in patients who were enrolled in 1 of 5 single-arm clinical trials. The ORR was 39.6% among 149 patients with 15 different tumor types (95% confidence interval, 31.7-47.9), with a 7% complete response rate. The duration of response ranged from 1.6+ months to 22.7+ months, with 78% of responses lasting ≥6 months. Overall, the adverse event profile of pembrolizumab was similar to the adverse event profile observed across prior trials that supported the approval of pembrolizumab in other indications. This approval of pembrolizumab is the first time that the FDA has approved a cancer treatment for an indication based on a common biomarker rather than the primary site of origin.

• Authors: Leigh Marcus, Steven J Lemery, Patricia Keegan, Richard Pazdur
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 25 Issue 13 Pg. 3753-3758 (07 01 2019) ISSN: 1557-3265 [Electronic] United States
• PMID: 30787022 (Publication Type: Journal Article)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• pembrolizumab

Topics

• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Agents, Immunological (administration & dosage, adverse effects, therapeutic use)
• Clinical Trials as Topic
• DNA Mismatch Repair (drug effects)
• Drug Approval
• Drug and Narcotic Control
• Humans
• Kaplan-Meier Estimate
• Microsatellite Instability
• Molecular Targeted Therapy (adverse effects, methods)
• Neoplasms (drug therapy, genetics, mortality, pathology)
• Prognosis
• Treatment Outcome
• United States
• United States Food and Drug Administration