对于晚期表皮生长因子受体 (EGFR) 突变的非小细胞肺癌 (NSCLC) 患者，推荐的一线治疗是 EGFR 酪氨酸激酶抑制剂 (EGFR-TKI)。 BRAF 改变已被确定为耐药机制。我们的目的是确定此类患者的特征和后续治疗策略。我们对携带获得性 BRAF 改变的 NSCLC 患者进行了系统的文献综述。此外，还对四川大学华西医院接受 EGFR-TKI 治疗后进展的 BRAF 改变的 NSCLC 患者进行了筛查。分析了患者特征、治疗方案和结果。总共纳入 104 名患者，其中 2 名来自我们中心。 75 名患者 (72.1%) 携带 BRAF 突变（57 名 I 类突变、7 名 II 类突变、9 名 III 类突变和 2 名非 I-III 突变），29 名患者 (27.9%) 携带 BRAF 融合。 18 名患者接受了三靶向治疗，包括先前的 EGFR-TKIs 加达拉非尼和曲美替尼，23 名患者接受了其他治疗。接受三靶点治疗的患者的中位无进展生存期明显长于接受其他治疗的患者（8.0 个月与 2.5 个月，P < 0.001）。在 BRAF 突变患者中观察到类似的结果（9.0 个月与 2.8 个月，P = 0.004），特别是在 BRAF I 类突变患者中（9.0 个月与 2.5 个月，P < 0.001）。在 BRAF 融合患者中也观察到了潜在的益处（5.0 个月与 2.0 个月，P = 0.230）。 20 名患者（48.8%）经历了不良事件。 5 名患者 (12.2%) 需要减少 RAF 或 MEK 抑制剂的剂量。 5 名患者 (12.2%) 永久停止治疗（3 名接受三靶向治疗；1 名接受既往 EGFR-TKI 加维莫非尼；1 名患者接受既往 EGFR-TKI 加曲美替尼）。 BRAF 改变，特别是 BRAF 突变和 BRAF 融合，促进对 EGFR 的耐药性-TKIs。三靶向治疗对于患有获得性 BRAF 改变的 EGFR 突变 NSCLC 患者有效且安全，主要是在 BRAF I 类突变患者和潜在的 BRAF 融合患者中。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

The recommended first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients is EGFR-tyrosine kinase inhibitors (EGFR-TKIs). BRAF alterations have been identified as resistance mechanisms. We aimed to identify features of and subsequent treatment strategies for such patients.We conducted a systematic literature review of NSCLC patients harboring acquired BRAF alterations. Additionally, BRAF-altered NSCLC patients who progressed from EGFR-TKIs at West China Hospital of Sichuan University were screened. Patient characteristics, treatment options, and outcomes were analyzed.A total of 104 patients were included, 2 of whom came from our center. Seventy-five patients (72.1%) harbored BRAF mutations (57 class I mutations, 7 class II mutations, 9 class III mutations, and 2 non-class I-III mutations), and 29 (27.9%) harbored BRAF fusions. Eighteen patients received triple-targeted therapy, including prior EGFR-TKIs plus dabrafenib and trametinib, and 23 patients received other treatments. The median progression-free survival was significantly longer in patients receiving triple-targeted therapy than in those receiving other treatments (8.0 versus 2.5 months, P < 0.001). Similar findings were observed in patients with BRAF mutations (9.0 versus 2.8 months, P = 0.004), particularly in those with BRAF class I mutations (9.0 versus 2.5 months, P < 0.001). A potential benefit was also observed among patients with BRAF fusions (5.0 versus 2.0 months, P = 0.230). Twenty patients (48.8%) experienced adverse events. Dose reduction of RAF or MEK inhibitor was required in five patients (12.2%). Five patients (12.2%) permanently discontinued treatment (three on triple-targeted therapy; one on prior EGFR-TKI plus vemurafenib; one on prior EGFR-TKI plus trametinib).BRAF alterations, specifically BRAF mutations and BRAF fusions, facilitate resistance to EGFR-TKIs. Triple-targeted therapy is effective and safe for patients with EGFR-mutant NSCLC with acquired BRAF alterations, mainly among patients with BRAF class I mutations and potentially in patients with BRAF fusions.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.