University of Washington, Seattle, WA, USA.
Fred Hutchinson Cancer Center, Seattle, WA, USA.
Adv Ther. 2024 Jul;41(7):2586-2605. doi: 10.1007/s12325-024-02839-4. Epub 2024 May 2.
According to current guidelines, targeted therapy with a combination of BRAF plus MEK inhibitors is the preferred first-line treatment for patients with BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC). In the open-label, single-arm, phase 2 PHAROS trial (NCT03915951), the combination of encorafenib, a potent BRAF inhibitor, and binimetinib, a potent MEK inhibitor, demonstrated durable antitumor activity with a manageable safety profile in this patient population. On the basis of the results of this study, the combination of encorafenib plus binimetinib was approved by the US Food and Drug Administration on October 11, 2023, for patients with BRAF V600E-mutant metastatic NSCLC. In this review, we summarize the efficacy and safety of encorafenib plus binimetinib from the PHAROS study. In addition, we discuss strategies to manage adverse reactions with this combination therapy with the intent of minimizing unnecessary treatment discontinuations in these patients.
根据当前的指南,BRAF 加 MEK 抑制剂的靶向治疗是 BRAF V600E 突变型转移性非小细胞肺癌(NSCLC)患者的首选一线治疗。在开放标签、单臂、2 期 PHAROS 试验(NCT03915951)中,强效 BRAF 抑制剂恩考芬尼和强效 MEK 抑制剂比美替尼的联合治疗在该患者人群中显示出持久的抗肿瘤活性和可管理的安全性。基于这项研究的结果,恩考芬尼加比美替尼的联合治疗于 2023 年 10 月 11 日获得美国食品和药物管理局的批准,用于治疗 BRAF V600E 突变型转移性 NSCLC 患者。在这篇综述中,我们总结了 PHAROS 研究中恩考芬尼加比美替尼的疗效和安全性。此外,我们还讨论了管理这种联合治疗不良反应的策略,旨在尽量减少这些患者不必要的治疗中断。