FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non‐Small Cell Lung Cancer Whose Tumors Express Programmed Death‐Ligand 1. (29th March 2016)

• Record Type: Journal Article
• Authors: Sul, Joohee; Blumenthal, Gideon M.; Jiang, Xiaoping; He, Kun; Keegan, Patricia; Pazdur, Richard
• Is Part Of: Oncologist. Volume 21:Number 5(2016)
• Page Start: 643
• Page End: 650
• Publication Date: 2016-03-29
• Subjects: Lung cancer -- Pembrolizumab -- Programmed death‐ligand 1 -- U.S. Food and Drug Administration; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2015-0498
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : On October 2, 2015, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab, a breakthrough therapy‐designated drug, for the treatment of patients with metastatic non‐small cell lung cancer (NSCLC) whose tumors express programmed death‐ligand 1 (PD‐L1), as determined by an FDA‐approved test, and who have disease progression on or after platinum‐containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. This indication was approved concurrently with the PD‐L1 immunohistochemistry 22C3 pharmDx, a companion diagnostic test for patient selection based on PD‐L1 tumor expression. The accelerated approval was granted based on durable objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open‐label trial enrolling 550 patients with metastatic NSCLC. The efficacy population comprised 61 patients with tumors identified as strongly positive for PD‐L1, and the confirmed ORR as determined by blinded independent central review was 41% (95% confidence interval: 28.6%, 54.3%); all were partial responses. At the time of the analysis, responses were ongoing in 21 of 25 patients (84%), with 11 patients (44%) having response duration of ≥6 months. The most commonly occurring (≥20%) adverse reactions included fatigue, decreased appetite, dyspnea, and cough. The most frequent (≥2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. Immune‐mediated adverse reactions occurred in 13% of patients and included pneumonitis, colitis, hypophysitis, and thyroid disorders. The accelerated approval regulations describe approval of drugs and biologic products for serious and life‐threatening illnesses based on a surrogate endpoint likely to predict clinical benefit. Under these regulations, a confirmatory trial or trials is required to verify and describe the benefit of pembrolizumab for patients with metastatic NSCLC. Implications for Practice: This report presents key information on the U.S. Food and Drug Administration (FDA) accelerated approval of pembrolizumab for the treatment of patients with metastatic non‐small cell lung cancer whose tumors express programmed death‐ligand 1, as determined by an FDA‐approved test, and who have disease progression on or after platinum‐containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. The report discusses the data supporting the approval decision, specifically highlighting the incorporation of a companion diagnostic in the key study and the optimal dose of pembrolizumab. Abstract : The U.S. Food and Drug Administration granted accelerated approval to pembrolizumab for the treatment of patients with metastatic non‐small cell lung cancer whose tumors express programmed death‐ligand 1. This work discusses the data supporting the approval decision, specifically highlighting the incorporation of a companion diagnostic in the key study and the optimal dose of pembrolizumab.