V-Raf murine sarcoma viral oncogene homolog B (BRAF) kinase, which was encoded by BRAF gene, plays critical roles in cell signaling, growth, and survival. Mutations in BRAF gene will lead to cancer development and progression. In non-small cell lung cancer (NSCLC), BRAF mutations commonly occur in never-smokers, women, and aggressive histological types and accounts for 1%–2% of adenocarcinoma. Traditional chemotherapy presents limited efficacy in BRAF-mutated NSCLC patients. However, the advent of targeted therapy and immune checkpoint inhibitors (ICIs) have greatly altered the treatment pattern of NSCLC. However, ICI monotherapy presents limited activity in BRAF-mutated patients. Hence, the current standard treatment of choice for advanced NSCLC with BRAF mutations are BRAF-targeted therapy. However, intrinsic or extrinsic mechanisms of resistance to BRAF-directed tyrosine kinase inhibitors (TKIs) can emerge in patients. Hence, there are still some problems facing us regarding BRAF-mutated NSCLC. In this review, we summarized the BRAF mutation types, the diagnostic challenges that BRAF mutations present, the strategies to treatment for BRAF-mutated NSCLC, and resistance mechanisms of BRAF-targeted therapy.

Immune checkpoint inhibitors (ICIs) have greatly transformed the treatment and improved the prognosis for patients with non-small cell lung cancer (NSCLC) without driver gene alterations. However, the effects of ICI combination therapy in ROS1 fusion-positive NSCLC remains unclear. Herein, we present a case with ROS1 fusion-positive NSCLC treated with ICI plus chemotherapy. The patient achieved a continuous partial response (PR) to ICI plus chemotherapy and a more than 35 months progression free survival. This case demonstrates that ICI plus chemotherapy is a promising option for patients with ROS1 fusion-positive NSCLC.

Corrigendum: Case Report: Durable response to immuno-chemotherapy in a case of ROS1 fusion-positive advanced lung adenocarcinoma: A case report

The efficacy of immune checkpoint inhibitors (ICIs) combination regimens in BRAF mutant non-small cell lung cancers (NSCLCs) remains poorly explored. Immunotypes, including programmed death-ligand 1 (PD-L1) levels and tumor mutation burden (TMB), were evaluated. Objective response rate (ORR), disease control rate, progression-free survival (PFS), and overall survival (OS) of patients treated with ICI combination therapies were analyzed. A total of 150 patients conducted PD-L1 tests, wherein PD-L1 expression of 22 patients was greater than or equal to 50% (14.7%). Among the 38 TMB-evaluated patients, 28 had fewer than 10 mutations per megabase (73.7%). For patients treated with ICI combined regimens, median PFS was 6 months and median OS was 21.9 months. When stratified by treatment line, OS presented a significant difference (p=0.01), while PFS did not (p=0.40). The ORR for the treated patients was 36.7%. When stratified by BRAF mutation type, no differences were observed in PFS (p=0.74) and OS (p=0.94). Furthermore, no difference was found in PD-L1 expression (p = 0.06) or TMB (p=0.22) between the responders and non-responders. BRAF-mutant NSCLCs is associated with low levels of PD-L1 expression and low/intermediate TMB. ICIs combined therapies present promising activity and could provide an option for BRAF-mutated NSCLCs.