Vemurafenib Combination Therapy for <em>BRAF</em> -Mutated Melanoma
Posted: Monday, January 14, 2019
An early-phase study conducted by Minny Bhatty, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues found that combination therapy consisting of the BRAF inhibitor vemurafenib and chemotherapy seems to be well tolerated by patients with advanced melanoma and BRAF V600 mutations, regardless of previous treatment with BRAF or MEK inhibitors. In fact, with signals of anticancer activity demonstrated, the investigators believe further study of this combination in this setting is justified. Their preliminary study results were published in Cancer.
A total of 19 patients received vemurafenib (480–720 mg orally twice a day), carboplatin (AUC 5–6 intravenously every 3 weeks), and paclitaxel (100–135 mg/m2 intravenously every 3 weeks). Of the 19 patients, 13 had melanoma. The maximum tolerated dose was not reached; the last safe dose levels were 720 mg of vemurafenib twice a day, AUC 5 for carboplatin, and 135 mg/m2 of paclitaxel.
Dose-limiting toxicities were persistent grade 2 creatinine elevation, grade 3 transaminitis, and grade 4 thrombocytopenia. Neutropenia, thrombocytopenia, fatigue, and anemia were the grade 3 or higher non–dose-limiting toxicities that occurred in more than 2 patients.
Of the 19 patients, 5 (all with melanoma) had a partial or complete response. The duration of these responses ranged from 3.1 to 54.1 months. Of the 13 patients who had previously received a BRAF or MEK inhibitor, 4 had a partial or complete response. Those who had not previously received platinum therapy had a better response to the treatment than those who did.
Disclosure: The study authors’ disclosure information may be found at onlinelibrary.wiley.com.