The BRAF inhibitor dabrafenib has significant antitumor activity in patients with advanced BRAF V600E mutant non-small cell lung cancer (NSCLC) whose disease has progressed after chemotherapy, according to phase II data presented at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain.

“Reports of lung cancers bearing mutations in BRAF have generated considerable interest because these mutations may be associated with increased sensitivity to BRAF tyrosine-kinase inhibiting agents,” said lead author David Planchard, MD, PhD, pulmonary oncologist at the Gustav-Roussy Cancer Campus, Paris, France.

Planchard said studies suggest that activating BRAF mutations are present in approximately 2% of lung carcinomas, and approximately 80% of these are V600E mutations. The BRAF V600E mutations are frequently associated with shorter disease-free, overall survival, and lower response rates to platinum-based chemotherapy.

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This open-label phase II study involves patients with BRAF V600E mutant non-small cell lung cancer, treated with dabrafenib alone (150 mg twice daily). The primary end point is investigator-assessed overall response rate, with secondary end points of progression-free survival, duration of response, overall survival, safety and tolerability, and population pharmacokinetics.

Data from the 78 patients enrolled in the study showed an overall response rate of 32% in patients who had already received one or more prior treatments, and a disease control rate of 56% after 12 weeks of treatment. The median duration of response was 11.8 months, and among the six first-line patients, three of them had partial response to the treatment.

The safety profile with dabrafenib was similar to that observed with previous studies in melanoma, the most common adverse events being fever (36% of patients), asthenia (30%), hyperkeratosis (30%), loss of appetite (29%), nausea (27%), cough (26%), fatigue (26%), and skin papilloma (26%). Cutaneous squamous cell carcinomas, including keratoacanthoma, were also reported in 18% of patients.

Based on earlier interim efficacy and safety data from this study, dabrafenib received a Breakthrough Therapy designation in lung cancer from the FDA in January 2014.

In summary, Planchard said, “These findings establish dabrafenib as an effective treatment option for patients with previously treated advanced BRAF V600E non-small cell lung cancer.”