Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, the Netherlands.
J Clin Oncol. 2023 Jul 20;41(21):3700-3711. doi: 10.1200/JCO.23.00774. Epub 2023 Jun 4.
The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with -mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with -mutant metastatic non-small-cell lung cancer (NSCLC).
In this ongoing, open-label, single-arm, phase II study, patients with -mutant metastatic NSCLC received oral encorafenib 450 mg once daily plus binimetinib 45 mg twice daily in 28-day cycles. The primary end point was confirmed objective response rate (ORR) by independent radiology review (IRR). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival, time to response, and safety.
At data cutoff, 98 patients (59 treatment-naïve and 39 previously treated) with -mutant metastatic NSCLC received encorafenib plus binimetinib. Median duration of treatment was 9.2 months with encorafenib and 8.4 months with binimetinib. ORR by IRR was 75% (95% CI, 62 to 85) in treatment-naïve and 46% (95% CI, 30 to 63) in previously treated patients; median DOR was not estimable (NE; 95% CI, 23.1 to NE) and 16.7 months (95% CI, 7.4 to NE), respectively. DCR after 24 weeks was 64% in treatment-naïve and 41% in previously treated patients. Median PFS was NE (95% CI, 15.7 to NE) in treatment-naïve and 9.3 months (95% CI, 6.2 to NE) in previously treated patients. The most frequent treatment-related adverse events (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). TRAEs led to dose reductions in 24 (24%) and permanent discontinuation of encorafenib plus binimetinib in 15 (15%) patients. One grade 5 TRAE of intracranial hemorrhage was reported. Interactive visualization of the data presented in this article is available at the PHAROS dashboard (https://clinical-trials.dimensions.ai/pharos/).
For patients with treatment-naïve and previously treated -mutant metastatic NSCLC, encorafenib plus binimetinib showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.
在 BRAF 抑制剂encorafenib 与 MEK 抑制剂 binimetinib 联合治疗下，-突变型转移性黑色素瘤患者的临床疗效得到了证实，且安全性可以接受。我们评估了 encorafenib 与 binimetinib 联合治疗 -突变型转移性非小细胞肺癌（NSCLC）患者的疗效和安全性。
在这项正在进行的、开放标签、单臂、二期研究中，-突变型转移性 NSCLC 患者接受每日一次口服 encorafenib 450mg 加每日两次 binimetinib 45mg，每 28 天为一个周期。主要终点是独立影像学审查（IRR）确认的客观缓解率（ORR）。次要终点包括缓解持续时间（DOR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期、反应时间和安全性。
在数据截止时，98 例 -突变型转移性 NSCLC 患者（59 例初治和 39 例经治）接受了 encorafenib 加 binimetinib 治疗。encorafenib 和 binimetinib 的中位治疗持续时间分别为 9.2 个月和 8.4 个月。IRR 确认的初治患者的 ORR 为 75%（95%CI，62 至 85），经治患者为 46%（95%CI，30 至 63）；中位 DOR 不可评估（NE；95%CI，23.1 至 NE）和 16.7 个月（95%CI，7.4 至 NE），分别。初治患者 24 周时的 DCR 为 64%，经治患者为 41%。初治患者的中位 PFS 为 NE（95%CI，15.7 至 NE），经治患者为 9.3 个月（95%CI，6.2 至 NE）。最常见的治疗相关不良事件（TRAEs）是恶心（50%）、腹泻（43%）和疲劳（32%）。TRAEs 导致 24 例（24%）患者减少剂量，15 例（15%）患者永久停止 encorafenib 加 binimetinib 治疗。报告了 1 例 5 级 TRAE 为颅内出血。本文所呈现数据的交互可视化可在 PHAROS 仪表板（https://clinical-trials.dimensions.ai/pharos/）上获得。
对于初治和经治 -突变型转移性 NSCLC 患者，encorafenib 加 binimetinib 具有显著的临床获益，安全性与黑色素瘤获批适应证中的观察结果一致。
