# A Case of Metastatic Non-small Cell Lung Cancer with Rare BRAF p.L485_T488delinsF Mutation Treated with Dabrafenib and Trametinib

## TL;DR

This paper reports a rare case of lung cancer with a BRAF mutation that responded to a specific drug combination, offering insights for treating similar cases.

## Contribution

The paper presents a novel case of a rare BRAF mutation in NSCLC successfully treated with dabrafenib and trametinib.

## Key findings

- The patient with BRAF p.L485_T488delinsF mutation showed clinical improvement after treatment with dabrafenib and trametinib.
- This case highlights the potential efficacy of BRAF/MEK inhibitors in non-V600 BRAF-mutant NSCLC.
- The treatment led to a reduction in tumor burden and metastases as observed through imaging.

## Abstract

鼠类肉瘤病毒癌基因同源物B（v-Rafmurine sarcoma viral oncogene homolog B, BRAF）是最重要的原癌基因之一，是丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）/细胞外信号调节激酶（extracellular signal-regulated kinase, ERK）信号通路的关键调节因子。BRAF突变在非小细胞肺癌（non-small cell lung cancer, NSCLC）患者中的发生率为1.5%-5.5%，其中BRAF V600突变占所有BRAF突变的30%-50%，BRAF V600E是最常见的突变类型。目前，达拉非尼联合曲美替尼已被美国国立综合癌症网络（National Comprehensive Cancer Network, NCCN）、欧洲肿瘤内科学会（European Society of Medical Oncology, ESMO）、中国临床肿瘤学会（Chinese Society of Clinical Oncology, CSCO）等多个国内外指南推荐作为BRAF V600突变NSCLC的一线治疗选择。然而，针对BRAF非V600突变，目前尚无明确的靶向治疗推荐。尽管个案报道提示达拉非尼联合曲美替尼对部分BRAF非V600突变患者可能有效，但由于病例数量有限且缺乏大样本临床试验数据，其疗效和安全性仍需进一步验证。本文报道了1例经达拉非尼联合曲美替尼治疗有效的罕见BRAF插入缺失突变（BRAF p.L485_T488delinsF）的NSCLC病例，旨在提高临床医生对该类罕见突变病例的认识，并为未来治疗策略的探索提供参考。

A: Right hilar and mediastinal mass; B: Subcutaneous metastatic nodule; C: Pancreatic tail and adrenal glands metastases; D: Right parieto-occipital region metastasis.

A-C: Baseline chest CT and brain MRI (March 10, 2024); D-F: Chest CT and brain MRI after 2 cycles of chemotherapy combined with immunotherapy (May 5, 2024); G-I: Chest CT and brain MRI at first disease progression (July 13, 2024); J, K: Chest CT following second-line targeted therapy (August 6, 2024); L: Brain MRI after second-line targeted therapy and cranial radiotherapy (September 12, 2024). CT: computed tomography; MRI: magnetic resonance imaging.

A: HE staining (×100); B: IHC staining for PD-L1 (×100); C: IHC staining for TTF-1 (×100); D: IHC staining for NapsinA (×100); E: IHC staining for p40 (×100); F: IHC staining for CK5/6 (×100). HE: hematoxylin-eosin; IHC: immunohistochemistry; PD-L1: programmed death-ligand 1; TTF-1: thyroid transcription factor-1; CK5/6: cytokeratin 5/6.