Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis

Abstract

and reports receiving grants from Eli Lilly and Bristol-Myers Squibb. Zhang reports employment for Novartis. Tan reports employment for Novartis. Gasal reports employment for Novartis. Santarpia reports employment for Novartis. Dr. Johnson reports receiving grants from Cannon Medical Systems, grants and personal fees from Novartis, and personal fees from Hengrui Therapeutics, Daiichi Sankyo, Checkpoint Therapeutics, Lilly, and G1 Therapeutics; has a patent EGFR Mutation Testing with royalties. Hashemi declares no conflict of interest.

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer

“…In BRAF mutant malignancies, treatment with BRAF inhibitors lead to amplification or activating of mutations that restore downstream MAPK signaling [ 65 ]. In NSCLC, adding a downstream MEK inhibitor to BRAF inhibitors improved duration of responses from 6.3 months to 10.2 months [ 26 , 66 ].…”

Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC

“…Dabrafenib and trametinib are inhibitors of BRAF and MEK, respectively, and their combination (dabrafenib plus trametinib [dab-tram]) is the only approved treatment for patients with BRAF V600 -mutated aNSCLC. 16 , 17 , 18 , 19 The clinical utility of dab-tram in BRAF V600E -mutated aNSCLC has been revealed in a noncomparative open-label, phase 2 trial, which reported overall response rates of 64% in treatment-naive patients, 20 and 63.2% in pretreated patients, 21 with a median overall survival (OS) of 17.3 months and 18.2 months, 22 respectively. Dab-tram was well tolerated and had a safety profile similar to that previously reported in patients with BRAF V600 -mutant metastatic melanoma.…”

EGFR/BRAF/MEK co-inhibition for EGFR-mutated lung adenocarcinoma patients with an acquired BRAFV600E mutation: a case report and review of literature

“…Based on these results, in 2017, the Food and Drug Administration approved dabrafenib and trametinib for first-line treatment of metastatic NSCLC patients harboring BRAF V600E mutation. The update of a phase 2 study (NCT01336634) showed promising efficacy of dabrafenib plus trametinib as second-line treatment, with a median PFS of 10.2 months and a median OS of 18.2 months [ 23 ] . However, no clinical trial has been conducted to confirm the efficacy of EGFR/BRAF/MEK co-inhibition in patients harboring E19 and BRAF V600E after the therapy of osimertinib.…”