title: FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation.
abstract: On August 17, 2011, the U.S. Food and Drug Administration (FDA) approved vemurafenib tablets (Zelboraf, Hoffmann-LaRoche Inc.) for the treatment of patients with unresectable or metastatic melanoma with the BRAF(V600E) mutation as detected by an FDA-approved test. The cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems, Inc.) was approved concurrently. An international, multicenter, randomized, open-label trial in 675 previously untreated patients with BRAF(V600E) mutation-positive unresectable or metastatic melanoma allocated 337 patients to receive vemurafenib, 960 mg orally twice daily, and 338 patients to receive dacarbazine, 1,000 mg/m(2) intravenously every 3 weeks. Overall survival was significantly improved in patients receiving vemurafenib [HR, 0.44; 95% confidence interval (CI), 0.33-0.59; P < 0.0001]. Progression-free survival was also significantly improved in patients receiving vemurafenib (HR, 0.26; 95% CI, 0.20-0.33; P < 0.0001). Overall response rates were 48.4% and 5.5% in the vemurafenib and dacarbazine arms, respectively. The most common adverse reactions (≥30%) in patients treated with vemurafenib were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, and nausea. Cutaneous squamous cell carcinomas or keratoacanthomas were detected in approximately 24% of patients treated with vemurafenib. Other adverse reactions included hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, QT prolongation, and liver enzyme laboratory abnormalities.
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. Geoffrey.Kim@fda.hhs.gov.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kim
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: McKee
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Yang-Min
authors.initials: YM
authors.lastname: Ning
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Maitreyee
authors.initials: M
authors.lastname: Hazarika
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Marc
authors.initials: M
authors.lastname: Theoret
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: John R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Qiang Casey
authors.initials: QC
authors.lastname: Xu
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Office of In Vitro Diagnostics and Radiological Health, Center for Devices and Radiologic Health, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Donna
authors.initials: D
authors.lastname: Roscoe
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: W David
authors.initials: WD
authors.lastname: McGuinn
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Whitney S
authors.initials: WS
authors.lastname: Helms
authors.affiliation: Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Russell
authors.affiliation: Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Sarah Pope
authors.initials: SP
authors.lastname: Miksinski
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Jeanne Fourie
authors.initials: JF
authors.lastname: Zirkelbach
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Justin
authors.initials: J
authors.lastname: Earp
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Amna
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf