恩考芬尼联合比尼替尼治疗BRAFV600突变转移性非小细胞肺癌患者II期非盲研究

SCI

19 June 2023

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer

(Journal of clinical oncology, IF: 50.717)

Riely GJ, Smit EF, Ahn MJ, Felip E, Ramalingam SS, Tsao A, Johnson M, Gelsomino F, Esper R, Nadal E, Offin M, Provencio M, Clarke J, Hussain M, Otterson GA, Dagogo-Jack I, Goldman JW, Morgensztern D, Alcasid A, Usari T, Wissel P, Wilner K, Pathan N, Tonkovyd S, Johnson BE. Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. J Clin Oncol. 2023 Jun 4:JCO2300774. doi: 10.1200/JCO.23.00774. Epub ahead of print. PMID: 37270692.

CORRESPONDING AUTHOR：Gregory J. Riely, MD, PhD, Memorial Sloan Kettering Cancer Center, 530 East 74th St, New York, NY 10021; Twitter: @RielyMD; e-mail: rielyg@MSKCC.ORG.

Purpose 目的

The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAFV600E/K-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC).

在BRAFV600E/K突变的转移性黑色素瘤患者中，恩考芬尼（BRAF抑制剂）加比尼替尼（MEK抑制剂）的组合已显示出临床疗效和可接受的安全性。我们评估了恩考芬尼联合比尼替尼对BRAFV600E突变的转移性非小细胞肺癌（NSCLC）患者的疗效和安全性。

Methods 方法

In this ongoing, open-label, single-arm, phase II study, patients with BRAFV600E-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.

在这项正在进行的非盲单臂II期研究中，BRAFV600E突变的转移性NSCLC患者接受口服恩考芬尼450毫克，每天一次，加上比尼替尼45毫克，每天两次，28天一个周期。主要终点是经独立放射学审查（IRR）确认的客观反应率（ORR）。次要终点包括反应持续时间（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。

Results 结果

At data cutoff, 98 patients (59 treatment-naïve and 39 previously treated) with BRAFV600E-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/).

在数据截止时，98名BRAFV600E突变的转移性NSCLC患者（59名以前未接受治疗，39名曾接受治疗）接受了恩考芬尼联合比尼替尼治疗。恩考芬尼的中位治疗时间为9.2个月，比尼替尼为8.4个月。按IRR计算，以前未接受治疗的患者的ORR为75%（95%CI，62至85），曾接受治疗的患者的ORR为46%（95%CI，30至63）；中位DOR分别为不可估计（NE；95%CI，23.1至NE）和16.7个月（95%CI，7.4至NE）。24周后，以前未接受治疗的患者的DCR为64%，曾接受治疗的患者为41%。以前未接受治疗的患者的中位PFS为NE（95%CI，15.7至NE），以前接受治疗的患者为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名（24%）患者减少剂量，15名（15%）患者永久停止使用恩考芬尼加比尼替尼。有1例颅内出血的5级TRAE报告。本文介绍的数据交互式可视化可在PHAROS面板（https:// clinical-trials.dimensions.ai/pharos/）上查看。

Conclusions 结论  

For patients with treatment-naïve and previously treated BRAFV600E-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.

对于以前未接受治疗和曾接受过治疗的BRAFV600E突变的转移性NSCLC患者，恩考芬尼联合比尼替尼显示出有意义的临床效益，其安全性与黑色素瘤的批准适应症中观察到的一致。

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