Zeng Ran, Luo Lifeng, Sun Xianwen, Bao Zhiyao, Du Wei, Dai Ranran, Tang Wei, Gao Beili, Xiang Yi
Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai 200025, China.
Cancer Drug Resist. 2021 Dec 1;4(4):1019-1027. doi: 10.20517/cdr.2021.98. eCollection 2021.
Despite the promising initial anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), most advanced non-small-cell lung cancers (NSCLCs) progress eventually due to therapeutic resistance. V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation has been considered as an uncommon mutation that contributes to acquired resistance for EGFR-TKIs. In the presented case, BRAF mutation was detected as an acquired resistance-mediated mutation in a patient treated with osimertinib (a third-generation EGFR-TKI). The presented patient achieved partial regression and ongoing PFS of four months after the co-inhibition of osimertinib plus dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Our case further enriches the clinical evidence of the efficacy of EGFR/BRAF/MEK co-inhibition in patients with an acquired BRAF mutation, consistent with the review of the literature (eight cases). Additionally, our case highlights the important role of sample type, method, and platform of gene detection in patient management, life quality, and prognosis, as well as the understanding of acquired resistance mechanism.
尽管表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）最初具有良好的抗肿瘤疗效，但大多数晚期非小细胞肺癌（NSCLCs）最终仍会因治疗耐药而进展。V-Raf鼠肉瘤病毒癌基因同源物B1（BRAF）突变被认为是一种罕见的突变，它会导致对EGFR-TKIs产生获得性耐药。在本病例中，BRAF突变被检测为一名接受奥希替尼（第三代EGFR-TKI）治疗的患者中由获得性耐药介导的突变。该患者在奥希替尼联合达拉非尼（BRAF抑制剂）和曲美替尼（MEK抑制剂）共同抑制后实现了部分缓解，并持续无进展生存期达四个月。我们的病例进一步丰富了EGFR/BRAF/MEK共同抑制对具有获得性BRAF突变患者疗效的临床证据，与文献综述（8例）一致。此外，我们的病例突出了基因检测的样本类型、方法和平台在患者管理、生活质量和预后以及对获得性耐药机制理解方面的重要作用。
