Dabrafenib plus trametinib may be a promising novel treatment that is safe and effective for treatment-naive patients with BRAFV600E–mutation positive non–small cell lung cancer (NSCLC), according to a study published in The Lancet Oncology.1
Current therapies such as immune-checkpoint inhibitors alone or in combination chemotherapy lead to good outcomes in patients with NSCLC, but nearly 50% of patients do not respond to treatment.
Results from 2 other cohorts of this phase 2 study (ClinicalTrials.gov Identifier: NCT01336634) demonstrated that genotype-directed therapy with dabrafenib plus trametinib was effective in previously treated patients with BRAFV600E-mutant NSCLC.
Thirty-six previously untreated patients were assigned to receive oral dabrafenib 150 mg twice daily plus oral trametinib 2 mg once daily until disease progression or unacceptable adverse events (AE). Radiological assessments were performed at baseline, at week 6, and every 6 weeks until week 36, then every 3 months.
At a median follow-up of 15.9 months, the overall response rate (ORR) was 64% (23 patients; 95% CI, 46-79), with 58% of patients achieving a partial response and 6% of patients achieving a complete response. The median duration of response (DoR) was 10.4 months. The ORR and DoR achieved by study patients with previously treated NSCLC in another cohort of this study were 67% and 9.8 months, respectively.
All patients experienced more than 1 AE, and 69% of patients experienced 1 or more grade 3 to 4 event. Serious reported AEs included pyrexia, ALT/AST elevations, and ejection fraction decrease.
The authors concluded that “as individualized treatment algorithms continue to be refined with the emergence of optimized sequencing strategies and new targeted therapeutic options, including dabrafenib and trametinib, outcomes in patients with NSCLC are likely to continue to improve.”
- Planchard D, Smit EF, Groen HJ, et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017 Sep 11. doi: 10.1016/S1470-2045(17)30679-4 [Epub ahead of print]