Targeted therapy for BRAF-mutation-positive advanced NSCLC

This trial aimed to determine whether dabrafenib (Tafinlar) was effective and safe in treating BRAF-mutation-positive advanced NSCLC. The authors concluded that dabrafenib had some anticancer ability and tolerable side effects compared to other treatment options available for this type of cancer.

Genetic mutations (changes) in the BRAF gene can allow cancer cells to grow and survive in the body. Patients with this type of mutation generally have shorter overall survival and a weaker response to chemotherapy. Certain targeted therapies, including dabrafenib, are used to block BRAF in melanoma cancers. Whether dabrafenib would be beneficial and safe in patients with BRAF-mutation-positive advanced non-small-cell lung cancer (NSCLC) remains to be determined.

This phase II trial included 84 patients with stage 4 (spread to other areas of the body) BRAF-mutation-positive NSCLC. 78 patients had been treated previously with chemotherapy while 6 were previously untreated. Each patient was treated with dabrafenib, and overall response (OR – tumor decrease by more than 30%) was reported.

The average OR in previously treated patients was 33%. In previously untreated patients the OR was 67%.  Disease progressed in 76% of patients, while 59% of patients had died by the final follow-up. Average overall survival (time from treatment until death from any cause) was 12.7 months.

99% of patients had at least 1 side effect, with 42% of these serious side effects. The most common serious side effects included physical weakness, squamous cell carcinoma, and basal cell carcinoma (two other forms of skin cancer). Less serious side effects included fever, chills and vomiting. 1 patient died due to the study drug.

The authors concluded that dabrafenib had anticancer activity and may be beneficial in patients with advanced BRAF-mutation-positive NSCLC. They suggest that the side effects are tolerable compared to side effects from other second and third line therapies.

This study was funded by GlaxoSmithKline, the manufacturers of dabrafenib, who were involved in the design of the trial as well as the data interpretation.