383P - Treatment outcomes with BRAF inhibitors with or without MEK inhibitors in advanced non-small cell lung cancer with positive BRAF mutation: A systematic review

Background

BRAF mutation is reported in about 1-5% cases of Non-small cell lung cancer (NSCLC). Although multiple phase II and retrospective studies have shown the effectiveness of single agent BRAF inhibition and combination BRAF/MEK inhibition in pre-treated and untreated patient populations; there is no phase III evidence. In this systematic review, we aimed to summarize the evidence so far in this setting.

Methods

A systematic search was carried out in PubMed, Medline, Embase and Cochrane database for articles published between January 2000 and February 2022. One author screened eligible studies, which met our pre-defined criteria, independently. Studies were assessed for design and quality, and a qualitative data synthesis was done.

Results

The search strategy resulted in 2952 articles. After two rounds of screening, 11 publications were included with total 655 patients. Median objective response rate (ORR) was 49% (range 33-71%). Median disease control rate (DCR) was 92.3% (range 78.9-100%). Median of duration of response was 9.7 months (range 6.4-15.2 months). The median of reported median progression free survival (PFS) was 6.5 months (range 1.2-17.5months). The median of reported median overall survival (OS) was 14 months (range 1.7-25.5 months). The response rates, duration of response and survival were better in studies reporting the outcomes of BRAF plus MEK inhibitors compared to studies with single agent BRAF inhibitors. The outcomes were also better in treatment naive patients compared to previously treated patients. Commonly reported grade ≥3 toxicities were hypertension, pyrexia, hyponatremia, neutropenia, dyspnoea, anaemia, altered liver function, asthenia, cutaneous epidermoid carcinoma.

Conclusions

BRAF inhibitor with or without MEK inhibitor therapy have shown promising clinical outcomes, with a manageable safety profile, in patients with BRAF mutant advanced NSCLC. Outcomes were better with combined treatment and in previously untreated patients. How these outcomes fare with emerging evidences and promising outcomes of Immunotherapy or chemotherapy-Immunotherapy combination; need further research in form of phase III trial.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.