TAFINLAR is indicated, in combination with trametinib, for...the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.

Dabrafenib plus trametinib in patients with previously untreated BRAF V600Emutant metastatic NSCLC

Dabrafenib plus trametinib is recommended (category 2A; preferred) for patients with BRAF V600E mutations. If combination therapy with dabrafenib/trametinib is not tolerated, single-agent therapy with dabrafenib or vemurafenib are "other recommended" agents.

...- Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (according to AJCC 8th edition) that is BRAF V600E mutation-positive by local test result from a qualified assay (NMPA and/or MOH-approved)...

...- Presence of a BRAF V600E mutation in lung cancer tissue....

This single-arm, open-label, multicentre, phase II study (NCT04452877) enrolled Chinese patients with BRAF V600E- mutation positive, stage IV NSCLC...to receive dabrafenib 150 mg twice daily plus trametinib 2 mg once daily….The ORR was 75% (95% confidence interval: 50.9-91.3) by both, central as well as investigator assessment...

Patients (pts) with advanced NSCLC harboring BRAF V600E mutation diagnosed between 01.01.2016 and 31.12.2019 and treated with D-T combination...Objective response rates were 73.8% [95% CI 65.5 - 82.2] and 82.9% [95% CI 71.4 - 94.4], disease progression was observed as best response in 3.7% [95% CI 0.1 - 7.3] and 0% in L2+ and L1, respectively....Our series confirms significant efficacy of D-T combination in BRAF V600E-mutated metastatic NSCLC.

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.

This retrospective multicentric study included 40 patients with advanced NSCLC harboring BRAF V600E mutation and receiving dabrafenib plus trametinib….For the 9 patients with first-line treatment, median PFS was 16.8 (95% CI 6.1-23.2) months and median OS was 21.8 (95% CI 1.0-not reached) months; for the 31 patients with second-line or more treatments, median PFS and OS were 16.8 (95% CI 6.1-23.2) months and 25.5 (95% CI 16.6-not reached) months, respectively.

Of 30 V600E-mutated patients who received anti-BRAF therapy during the course of disease, the median PFS of vemurafenib, dabrafenib, and dabrafenib plus trametinib was 7.8 months, 5.8 months and 6.0 months, respectively (P = 0.970)….Our data demonstrated the clinical benefit of anti-BRAF targeted therapy in Chinese NSCLC patients harboring BRAF-V600E mutation.

The phase II multicenter, open label study, which evaluated efficacy and safety of D+T in pretreated (cohort B) and treatment (tx)-naive (cohort C) pts with BRAF V600E mut metastatic NSCLC....median (m) follow-up was 16.3 mo in tx-naïve pts and 16.6 mo in pretreated pts.mOS was 17.3 mo (95% CI: 12.3, 40.2; 3 yr OS: 40%) and 18.2 mo (95% CI: 14.3, 28.6; 3 yr OS: 33%) with 14/36 and 11/57 pts alive in tx naïve and pretreated pts respectively....This update of BRF113928 study reported improved and durable OS rates with combination D+T in BRAF V600E mut NSCLC pts.

Enrolled patients received oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) in continuous 21-day cycles...36 patients (63·2% [95% CI 49·3-75·6]) achieved an investigator-assessed overall response….Dabrafenib plus trametinib could represent a new targeted therapy with robust antitumour activity and a manageable safety profile in patients with BRAF(V600E)-mutant NSCLC.

...case was subsequently treated with dabrafenib and trametinib combination and achieved a partial response lasting for more than 6 months. This is the first case reporting the treatment with dabrafenib and trametinib may serve as an effective option for later-line treatment for patients harboring resistant BRAF V600E.

Hence, we reported the first case of a patient with BM of lung papillary carcinoma harboring a BRAF V600E mutation who benefited from dabrafenib combined with trametinib, and following the development of the BRAF S365L mutation, vemurafenib remained an effective therapeutic option.