Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-year survival rates and genomic analysis

David Planchard, Benjamin Besse, Harry J M Groen, Sayed M S Hashemi, Julien Mazieres, Tae Min Kim, Elisabeth Quoix, Pierre-Jean Souquet, Fabrice Barlesi, Christina Baik, Liza C Villaruz, Ronan J Kelly, Shirong Zhang, Monique Tan, Eduard Gasal, Libero Santarpia, Bruce E Johnson

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Introduction: Dabrafenib plus trametinib was found to have robust antitumor activity in patients with BRAF V600E-mutant metastatic NSCLC (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-naive (cohort C) patients with BRAF V600E-mutant mNSCLC received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary end point was investigator-assessed overall response rate per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points were duration of response, progression-free survival, overall survival, and safety. Results: At data cutoff, 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, overall response rate (95% confidence interval [CI]) was 68.4% (54.8–80.1) and 63.9% (46.2–79.2), median progression-free survival (95% CI) was 10.2 (6.9–16.7) and 10.8 (7.0–14.5) months, and median overall survival (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-naive patients, respectively. A total of 17 patients (18%) 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 was found to have substantial and durable clinical benefit, with a manageable safety profile, in patients with BRAF V600E-mutant mNSCLC, regardless of previous treatment.

Original languageEnglish
Pages (from-to)103-115
Number of pages13
JournalJournal of thoracic oncology
Issue number1
Early online date26 Aug 2021
Publication statusPublished - Jan 2022


  • BRAF V600E
  • Dabrafenib
  • Genomic analysis
  • Non–small cell lung cancer
  • Trametinib

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