Wang Diming, Ye Wei, Yin Zihuan, Xu Ning, Ma Jie
Department of Oncology, Anhui Chest Hospital, Hefei, 230022, People's Republic of China.
Department of Pathology, Anhui Chest Hospital, Hefei, 230022, People's Republic of China.
Onco Targets Ther. 2025 Apr 13;18:539-544. doi: 10.2147/OTT.S512704. eCollection 2025.
Osimertinib has become the standard of care in the first-line treatment of advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although previous studies reported that the BRAF V600E mutation is a unique resistance mechanism to osimertinib, the treatment of lung adenocarcinoma patients harboring both EGFR and acquired BRAF-V600E comutations remains unclear. Here, we report a case of a 36-year-old woman diagnosed with stage IV lung adenocarcinoma harboring the EGFR L858R mutation. She received osimertinib for 24 months and experienced progressive disease. Rebiopsy pathology revealed that the lung lesion was still adenocarcinoma, and NGS revealed gains of BRAF V600E and TP53 mutations in addition to the EGFR L858R mutation. This patient subsequently received aumolertinib in combination with dabrafenib and trametinib and achieved a complete response for 8 months. In conclusion, acquired BRAF-V600E mutations may contribute to osimertinib resistance. Aumolertinib plus BRAF inhibitors improves outcomes in patients with EGFR-L858R and acquired BRAF-V600E comutant lung adenocarcinoma in whom osimertinib treatment has failed.
奥希替尼已成为携带表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌（NSCLC）一线治疗的标准方案。尽管先前的研究报道BRAF V600E突变是对奥希替尼独特的耐药机制，但对于同时携带EGFR和获得性BRAF-V600E共突变的肺腺癌患者的治疗仍不明确。在此，我们报告一例36岁女性，诊断为携带EGFR L858R突变的IV期肺腺癌。她接受了24个月的奥希替尼治疗，随后病情进展。再次活检病理显示肺部病变仍为腺癌，二代测序（NGS）显示除EGFR L858R突变外，还存在BRAF V600E和TP53突变。该患者随后接受了奥莫替尼联合达拉非尼和曲美替尼治疗，并实现了8个月的完全缓解。总之，获得性BRAF-V600E突变可能导致奥希替尼耐药。对于奥希替尼治疗失败的携带EGFR-L858R和获得性BRAF-V600E共突变的肺腺癌患者，奥莫替尼联合BRAF抑制剂可改善治疗结局。
