The results of BREAK-2, a phase II clinical trial of dabrafenib, were recently published in the Journal of Clinical Oncology, showing that the BRAF inhibitor dabrafenib was effective in the treatment of patients with advanced melanoma with the BRAF V600E/K mutation, with a manageable toxicity.
Based on the results of this study, and the subsequent BREAK-3 phase III trial, dabrafenib was approved by the FDA in late May for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation.
In addition to the drug’s efficacy, the researchers, led by Paolo A. Ascierto, MD, vice-director of the unit of melanoma, cancer immunotherapy and innovative therapy at the National Tumor Institute Fondazione G. Pascale, Naples, Italy, also found that circulating cell-free DNA could represent a possible predictive marker of response, if results are confirmed in a larger prospective study.
Ascierto and colleagues examined outcomes in 76 patients with stage IV BRAF V600E and 16 patients with stage IV BRAF V600K metastatic melanoma. All patients were assigned to receive 150 mg dabrafenib twice daily until progression, death, or unacceptable adverse events.
At the time of follow-up, 59% of patients in the BRAF V600E–mutated population had a confirmed response, including 7% with complete response. Of the patients with BRAF V600K–mutated melanoma, 13% had a partial response.
The researchers also looked at secondary endpoints of progression-free survival and overall survival. The progression-free survival in the V600E group was 6.3 months, and in the V600K group it was 4.5 months. The overall survival for V600E and V600K was 13.1 months and 12.9 months, respectively.
“The overall survival reached in the study confirmed the important role of the BRAF inhibitor in the treatment of advanced melanoma patients,” Ascierto said.
Overall the treatment was considered to be well tolerated. Twenty-seven percent of the group experienced a serious adverse event and 93% of patients experienced any adverse event. The most commonly occurring adverse events were arthralgia (33%), hyperkeratosis (27%), and pyrexia (24%).
“The evaluation of the circulating cell-free DNA showed a possible correlation between the baseline level of circulating cell-free DNA in the V600E population and progression-free survival and response rate, with higher value of baseline circulating cell-free DNA correlating with a reduced progression-free survival and overall response rate,” Ascierto said. “Of course, this finding should be confirmed in further studies.”