(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, MD, 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, 150mg twice daily was recommended for Phase 2. At this dose, responses were seen in 69% of the patients with Val600 BRAF-mutant melanoma, including 50% with a confirmed response. Of the 27 patients with the Val600Glu BRAF mutation, 78% responded and 56% had a confirmed response. The responses were durable, and 47% 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.