Monday, May 21, 2012 (Last Updated: 05/22/2012)MONDAY, May 21 (HealthDay News) -- Dabrafenib, the mutant BRAF-selective inhibitor of BRAF kinase, is safe for treating solid tumors and shows antitumor activity against Val600-mutant BRAF melanomas and other solid tumors, including melanomas that have metastasized to the brain, according to a study published in the May 19 issue of The Lancet.
Gerald S. Falchook, M.D., from the University of Texas MD Anderson Cancer Center in Houston, and colleagues used an accelerated dose titration method with dabrafenib in a phase 1 trial of 184 adults with incurable solid tumors (156 with metastatic melanoma) to establish a recommended phase 2 dose. In phase 2, efficacy was assessed in 36 patients with Val600 BRAF-mutant metastatic melanoma, 10 patients with untreated brain metastases, and 28 patients with non-melanoma solid tumors.
The researchers found that, based on safety, pharmacokinetic, and response data, 150 mg twice daily was recommended for phase 2. At this dose, responses were seen in 69 percent of the patients with Val600 BRAF-mutant melanoma, including 50 percent with a confirmed response. Of the 27 patients with the Val600Glu BRAF mutation, 78 percent responded and 56 percent had a confirmed response. The responses were durable, and 47 percent of patients were treated for more than six months. Of the 10 melanoma patients with brain metastases, in nine cases the metastases shrunk. Dabrafenib also showed antitumor activity against BRAF-mutant non-melanoma solid tumors.
"Dabrafenib is safe in patients with solid tumors, and an active inhibitor of Val600-mutant BRAF with responses noted in patients with melanoma, brain metastases, and other solid tumors," Falchook and colleagues conclude.
Several authors and/or their institutions disclosed financial ties to pharmaceutical companies, including GlaxoSmithKline, which funded the study and manufactures dabrafenib.
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