Yamazaki Naoya, Sakata Hidenori, Iida Osamu, Katayama Teruaki, Uhara Hisashi
Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Pharmacovigilance, Ono Pharmaceutical Co., Ltd, Osaka, Japan.
Int J Clin Oncol. 2025 Apr;30(4):814-823. doi: 10.1007/s10147-025-02693-6. Epub 2025 Feb 7.
A BRAF inhibitor, encorafenib, combined with a MEK inhibitor, binimetinib, was approved in Japan in early 2019 for the treatment of BRAF V600-mutant, unresectable malignant melanoma based on results of the global phase III trial, COLUMBUS, conducted in various countries including Japan. This post-marketing surveillance (PMS) assessed the combination in real-world clinical practice in Japan.
We performed a prospective, multicentre, 12-month PMS of the safety and effectiveness of encorafenib plus binimetinib for radically unresectable, BRAF-mutant malignant melanoma in Japan.
Among 174 survey forms collected from 85 centres between February 2019 and August 2020, 172 were included for safety and effectiveness analysis. Patients (male [52.3%], median age 62.0 years) had Eastern Cooperative Oncology Group Performance Status 0 or 1 (91.8%) and comorbidities (55.2%). Respective encorafenib and binimetinib median dosages were 450 mg/day and 90 mg/day; median treatment duration, 24.1 and 24.2 weeks, and discontinuation, 71.5% for each, primarily for disease progression (56.9%) and adverse drug reactions (ADRs, 38.2%). Safety assessment ADRs occurred in 99 patients (57.6%), including eye disorders (40.7%), hepatic dysfunction (20.3%), rhabdomyolysis (4.7%), haemorrhage (2.3%), palmar-plantar erythrodysaesthesia syndrome (1.7%), and hypertension (1.7%); 19.8% were grade ≥ 3, none were grade 5, most resolved with/without treatment modification. At 12 months, the objective response rate was 48.8% (95% CI 41.2, 56.6; complete [19.2%], partial [29.7%]), overall survival was 40.1%.
The safety and effectiveness of encorafenib plus binimetinib in Japanese patients with BRAF-mutant malignant melanoma were similar to data reported in COLUMBUS; no new safety concerns were identified.
一种BRAF抑制剂恩考芬尼与一种MEK抑制剂比美替尼联合用药，基于在包括日本在内的多个国家进行的全球III期试验COLUMBUS的结果，于2019年初在日本获批用于治疗BRAF V600突变的不可切除恶性黑色素瘤。本次上市后监测（PMS）评估了该联合用药在日本真实世界临床实践中的情况。
我们对恩考芬尼加比美替尼治疗日本BRAF突变的不可切除恶性黑色素瘤的安全性和有效性进行了一项为期12个月的前瞻性、多中心PMS。
在2019年2月至2020年8月期间从85个中心收集的174份调查问卷中，172份纳入安全性和有效性分析。患者（男性占52.3%，中位年龄62.0岁）东部肿瘤协作组体能状态为0或1（91.8%）且有合并症（55.2%）。恩考芬尼和比美替尼的中位剂量分别为450毫克/天和90毫克/天；中位治疗持续时间分别为24.1周和24.2周，停药率均为71.5%，主要原因是疾病进展（56.9%）和药物不良反应（ADR，38.）。安全性评估99例患者（57.6%）出现ADR，包括眼部疾病（40.7%）、肝功能障碍（20.3%）、横纹肌溶解（4.7%）、出血（2.3%）、手足红斑感觉异常综合征（1.7%）和高血压（1.7%）；19.8%为≥3级，无5级，多数经调整治疗或未调整治疗后缓解。12个月时，客观缓解率为48.8%（95%CI 41.2，56.6；完全缓解[19.2%]，部分缓解[29.7%]），总生存率为40.1%。
恩考芬尼加比美替尼在日本BRAF突变恶性黑色素瘤患者中的安全性和有效性与COLUMBUS试验报告的数据相似；未发现新 的安全性问题。
