title: FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1.
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.
  
  
  
  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.
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA joohee.sul@fda.hhs.gov.
authors.forename: Joohee
authors.initials: J
authors.lastname: Sul
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Blumenthal
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D017277:Drug Approval; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C582435:pembrolizumab
keywords: Lung cancer; Pembrolizumab; Programmed death-ligand 1; U.S. Food and Drug Administration