Liu Yujie, Zeng Hao, Wang Ke, Li Yalun, Tian Panwen, Li Weimin
Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610041, Sichuan, China.
Department of Respiratory and Critical Care Medicine, Lung Cancer Treatment Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Lung Cancer. 2020 Aug;146:355-357. doi: 10.1016/j.lungcan.2020.06.004. Epub 2020 Jun 9.
BRAFG469A and V600E were reported as the mechanisms of acquired resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer patients. Here, we described a rare case of BRAF N581S after gefitinib resistance and response to BRAF inhibitor plus MEK inhibitor.
Next-generation sequencing (NGS) was performed on the tumor tissue and plasma samples of a patient with metastatic lung adenocarcinoma harboring EGFR exon 19 deletion (EGFR 19del).
EGFR 19del and MET amplification was detected after resistance to the initial gefitinib therapy. After 9 months of treatment with gefitinib plus crizotinib, the disease progressed again. NGS revealed the known EGFR 19del and a BRAF N581S missense mutation after progression. The patient obtained durable clinical benefit upon treatment with dabrafenib plus trametinib, achieving a progression-free survival (PFS) of more than 33 months.
BRAF N581S mutation could be explored as one kind of mechanism of acquired resistance to EGFR-TKIs. Combined inhibition of BRAF and MEK is a potential therapeutic strategy.
BRAF G469A和V600E被报道为非小细胞肺癌患者对第一代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）获得性耐药的机制。在此，我们描述了1例吉非替尼耐药后出现BRAF N581S突变且对BRAF抑制剂加MEK抑制剂有效的罕见病例。
对1例携带EGFR外显子19缺失（EGFR 19del）的转移性肺腺癌患者的肿瘤组织和血浆样本进行二代测序（NGS）。
在对初始吉非替尼治疗耐药后检测到EGFR 19del和MET扩增。在吉非替尼加克唑替尼治疗9个月后，疾病再次进展。NGS显示疾病进展后存在已知的EGFR 19del和BRAF N581S错义突变。该患者接受达拉非尼加曲美替尼治疗后获得持久的临床获益，无进展生存期（PFS）超过33个月。
BRAF N581S突变可作为EGFR-TKIs获得性耐药的一种机制进行探索。联合抑制BRAF和MEK是一种潜在的治疗策略。
