Scientific Publications by FDA Staff

Clin Cancer Res 2014 Oct 1;20(19):4994-5000

FDA approval summary: vemurafenib for treatment of unresectable or metastatic melanoma with the BRAFV600E mutation.

Kim G, McKee AE, Ning YM, Hazarika M, Theoret M, Johnson JR, Xu QC, Tang S, Sridhara R, Jiang X, He K, Roscoe D, McGuinn WD, Helms WS, Russell AM, Pope Miksinski S, Fourie Zirkelbach J, Earp J, Liu Q, Ibrahim A, Justice R, Pazdur R

On August 17, 2011, the 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(R) 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 1000 mg/m2 intravenously every 3 weeks. Overall survival (OS) was significantly improved in patients receiving vemurafenib [hazard ratio (HR) 0.44; 95% CI, 0.33-0.59; p< 0.0001)]. Progression-free survival (PFS) was also significantly improved in patients receiving vemurafenib (HR 0.26; 95% CI, 0.20-0.33; p<0.0001). Overall response rates (ORR) 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 (cuSCC) 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.