Dabrafenib Active in BRAF-Mutant Metastatic NSCLC


Key Points

  • Dabrafenib produced responses in both previously treated and untreated patients with BRAF-mutant metastatic NSCLC.
  • In previously treated patients, the response occurred in 33%, and disease control was accomplished in 58%.

Planchard et al found that the BRAF kinase inhibitor dabrafenib (Tafinlar) produced responses in previously treated and untreated patients with BRAF-mutant metastatic non–small cell lung cancer (NSCLC), according to a phase II trial reported in The Lancet Oncology. Activating BRAF V600E mutations are found in approximately 1% to 2% of lung adenocarcinomas.

Study Details

In the trial, 84 patients, including 6 without previous systemic treatment, received oral dabrafenib at 150 mg twice daily. Patients had a mean age of 66 years, 50% were female, 76% were white and 22% Asian, and 37% were never-smokers; the number of previous systemic regimens was one for 51%, two for 18%, and three for 31%.

Response Rates

Response was achieved in 26 (33%) of the 78 previously treated patients, with stable disease in an additional 19 (24%), and in 4 (75%) of the 6 previously untreated patients. Median duration of response was 9.6 months in previously treated patients and ranged from 3.2 to 12.5 months in previously untreated patients. Progression-free survival was a median of 5.5 months in the previously treated group and ranged from 4.0 to 16.6 months in previously untreated patients.

Adverse Events

The most common grade ≥ 3 adverse events were cutaneous squamous cell carcinoma (12%), asthenia (5%), and basal cell carcinoma (5%). Serious adverse events occurred in 42%. One patient died of intracranial hemorrhage considered to be related to dabrafenib treatment.

The investigators concluded: “Dabrafenib showed clinical activity in BRAF V600E–positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options.”

The study was funded by GlaxoSmithKline.

Bruce E. Johnson, MD, of Dana-Farber Cancer Institute, is the corresponding author of The Lancet Oncology article. 

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