In an early-phase study of dabrafenib, given alone or in combination with another targeted treatment, the drug has been shown to be safe and may be effective for patients with advanced melanoma, melanoma with brain metastases, and other solid tumors with the BRAF gene mutation.
The phase I study included 184 patients with melanoma or advanced solid tumors. Of these, 179 patients had tumors with BRAF mutations. The patients received varying amounts of oral dabrafenib to establish a safe, tolerable dose for use in further studies.
Of the 36 patients with BRAF-mutated metastatic melanoma with no brain metastases who received 150 mg of dabrafenib twice a day (the recommended phase II dose), half had a partial or complete response, according to the researchers. Most of the patients developed drug resistance, with a median time to disease progression of 5.5 months.
Dabrafenib led to partial responses in patients with papillary thyroid and non-small cell lung cancers, as well as in one patient with colorectal cancer. Seven other patients with colorectal cancer, one patient with ovarian cancer, and another with a gastrointestinal stromal tumor had stable disease. The 150 mg dose of dabrafenib twice per day also shrank asymptomatic brain lesions in 9 out of 10 patients with advanced melanoma, completely eliminating them in four of the patients. The median time to disease progression for patients with brain metastases was 4.2 months. All 10 patients were alive at five months, and two survived beyond a year. Patients with brain metastases typically survive for fewer than five months.