FDA Approves Pembrolizumab for First Tissue/Site-Agnostic Indication


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Richard Pazdur, MD

Richard Pazdur, MD

On May 23, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Keytruda) for 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 or with MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

This is the FDA’s first tissue/site-agnostic approval, ie, the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.

“This is an important first for the cancer community,” said Richard Pazdur, MD, Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and Director of the FDA’s Oncology Center of Excellence. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”

Approval Based on Five Trials

The approval was based on data from 149 patients with microsatellite instability–high or mismatch repair deficient solid tumors -cancers enrolled across five uncontrolled, multicohort, multicenter, single-arm clinical trials. Ninety patients had colorectal cancer and 59 patients were diagnosed with 1 of 14 other cancer types. Patients -received either pembrolizumab, 200 mg every 3 weeks, or pembrolizumab, 10 mg/kg every 2 weeks. Treatment continued until unacceptable toxicity, or disease progression that was either symptomatic, rapidly progressive, required urgent intervention, or associated with a decline in performance status. A maximum of 24 months of treatment was administered.

The major efficacy outcome measures were objective response rate ( by blinded independent central radiologists’ review according to RECIST 1.1), and response duration. The objective response rate was 39.6%. Responses lasted 6 months or more for 78% of those who responded to pembrolizumab. There were 11 complete responses and 48 partial responses. Objective response rate was similar irrespective of whether patients were diagnosed with colorectal cancer (36%) or a different cancer type (46% across the 14 other cancer types).

The most common adverse reactions to pembrolizumab include fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea. ■


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