BRAF inhibitors with or without MEK inhibitors in advanced BRAF-positive non-small cell lung cancer: A systematic review

Abstract

Objective

About 1% to 5% of cases of non-small cell lung cancer (NSCLC) have been found to have a BRAF mutation. There is no phase III data, despite the fact that numerous phase II and retrospective studies have demonstrated the efficacy of single agent BRAF inhibition and combination BRAF/MEK inhibition in patient groups that have received treatment and those who have not. Our goal in this systematic review was to provide an overview of the available evidence in this context.

Data Sources

A thorough search was conducted in the PubMed, Medline, Embase, and Cochrane databases for English-language papers published between January 2000 and December 2023 that had full text accessibility. Independently, one author screened the eligible studies that fit our predetermined requirements. A synthesis of the qualitative data was conducted, and the design and quality of the studies were evaluated.

Data Summary

There were 2952 articles found using the search method. Twelve publications with a total of 753 patients were included after two rounds of screening. 33–75% was the objective response rate (ORR). 64–100% was the disease control rate (DCR). The time span for the answer varied from 6.4 to 16.7 months. The range of the median progression-free survival (PFS) was 1.2 to 17.5 months. The range of the median overall survival (OS) was 1.7–25.5 months. When comparing studies with single agent BRAF inhibitors to those reporting the results of BRAF plus MEK inhibitors, the response rates, duration of response, and survival were better in the former case. When untreated patients receiving BRAF/MEK inhibitor therapy were compared to previously treated patients, the results were also improved. Hypertension, pyrexia, hyponatremia, neutropenia, dyspnoea, anaemia, abnormal liver function, asthenia, and cutaneous epidermoid carcinoma were among the frequently reported grade ≥3 toxicity.

Conclusions

Patients with advanced NSCLC that include a BRAF mutation have demonstrated encouraging clinical outcomes with a manageable safety profile when treated with BRAF inhibitors, either in combination with or without MEK inhibitor therapy. In patients who had not received treatment before, combination treatment produced greater results.