INTRODUCTION: Dabrafenib plus trametinib demonstrated robust antitumour activity in patients with BRAF V600E-mutant metastatic non-small cell lung cancer (mNSCLC). We report updated survival analysis of a phase 2 study (NCT01336634) with a minimum of 5-year follow-up and updated genomic data.
METHODS: Pretreated (cohort B) and treatment-naïve (cohort C) patients with BRAF V600E-mutant mNSCLC received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary endpoint was investigator-assessed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumours version 1.1. Secondary endpoints were duration of response, progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: At data cut-off, for cohorts B (57 patients) and C (36 patients), the median follow-up was 16.6 (range, 0.5-78.5) and 16.3 (range, 0.4-80) months, ORR (95% CI) was 68.4% (54.8-80.1) and 63.9% (46.2-79.2), median PFS (95% CI) was 10.2 (6.9-16.7) and 10.8 (7.0-14.5) months, and median OS (95% CI) was 18.2 (14.3-28.6) and 17.3 (12.3-40.2) months, respectively. The 4- and 5-year survival rates were 26% and 19% in pretreated patients and 34% and 22% in treatment-naïve patients, respectively. Seventeen (18%) patients were still alive. The most frequent adverse event was pyrexia (56%). Exploratory genomic analysis indicated that the presence of coexisting genomic alterations might influence clinical outcomes in these patients; however, these results require further investigation.
CONCLUSIONS: Dabrafenib plus trametinib therapy demonstrated substantial and durable clinical benefit, with a manageable safety profile, in patients with BRAF V600E-mutant mNSCLC, regardless of prior treatment.