Vemurafenib (RG67204, PLX4032): a potent, selective BRAF kinase inhibitor.
Vemurafenib is a potent inhibitor of the mutated BRAF kinase. Phase I and II clinical trials of vemurafenib showed response rates of more than 50% in patients with metastatic melanoma and BRAF mutation. A Phase III study comparing vemurafenib with dacarbazine in 675 previously untreated patients revealed overall survival to be 84% (95% CI: 78-89) in the vemurafenib group and 64% (95% CI: 56-73) in the dacarbazine group. Vemurafenib was associated with a relative reduction of 63% in the risk of death and 74% in the risk of either death or disease progression, as compared with dacarbazine (p < 0.001). Progression-free survival was longer in those treated with vemurafenib (median: 5.3 vs 1.6 months; hazard ratio: 0.26; 95% CI: 0.20-0.33). Response rates were 48% for vemurafenib and 5% for dacarbazine. After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended.
Vanderbilt-Ingram Cancer Center, Division of Hematology-Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232-6307, USA.
Samit
S
Patrawala
Igor
I
Puzanov
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077484:Vemurafenib
D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf