Efficacy of encorafenib plus binimetinib in patients with BRAF-mutated melanoma brain metastases: Results from the Dutch Melanoma Treatment Registry

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-05-19 DOI:10.1016/j.ejca.2025.115514

M. Bloem , K.P.M. Suijkerbuijk , M.J.B. Aarts , F.W.P.J. van den Berkmortel , C.U. Blank , W.A.M. Blokx , M.J. Boers-Sonderen , C.D.M. Boreel , J.W.B. de Groot , J.B.A.G. Haanen , G.A.P. Hospers , E. Kapiteijn , O.J. van Not , D. Piersma , B. Rikhof , A.M. Stevense-den Boer , A.A.M. van der Veldt , G. Vreugdenhil , M.W.J.M. Wouters , A.J.M. van den Eertwegh

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Abstract

Aim

Data on the effectiveness of encorafenib/binimetinib in melanoma patients with brain metastases (BMs) are limited.

Methods

All patients with BRAF V600-mutated melanoma and BMs treated with encorafenib/binimetinib between 2019 and 2022 in the Netherlands were included from the nationwide Dutch Melanoma Treatment Registry. Patients previously treated with other BRAF/MEK inhibitors were excluded. We analyzed objective response rates (ORR), progression-free survival (PFS), and overall survival (OS). Multivariable Cox regression identified factors associated with survival. Subgroup analyses included asymptomatic versus symptomatic BMs and line of treatment (first-line versus later-line).

Results

In total, 190 patients were included. Symptomatic BMs were present in 63 % of patients. Encorafenib/binimetinib was the first-line treatment in 64 % of all patients, while 36 % had prior immunotherapy. Overall, the ORR was 69.4 %, median PFS was 5.5 months (95 %CI 4.9–6.2), and median OS 11.9 months (95 %CI 10.0–15.7). Age ≥ 70, ECOG PS ≥ 2, symptomatic BMs, and elevated LDH were significantly associated with worse survival. Patients with prior immunotherapy had a median PFS of 6.9 months (95 %CI 4.3–9.6) and OS of 17.9 months (95 %CI 13.7–31.2), while this was 4.9 months (95 %CI 4.3–5.5) and 10.1 months (95 %CI 8.1–13.0) in treatment-naïve patients. Median PFS and OS in patients with asymptomatic versus symptomatic BMs were 6.1 months (95 %CI 4.9–9.8) and 20.5 (95 %CI 14.0-NA) versus 5.3 months (95 %CI 4.9–6.3) and 10.7 (95 %CI 8.9–13.7), respectively.

Conclusions

Encorafenib/binimetinib has clinical activity in real-world melanoma patients with BMs. Their prognosis is determined by the presence of symptomatic BMs, age, ECOG PS, and LDH levels.

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恩科非尼联合比尼美替尼治疗braf突变黑色素瘤脑转移患者的疗效：来自荷兰黑色素瘤治疗登记处的结果

关于encorafenib/binimetinib在脑转移（BMs）黑色素瘤患者中的有效性的数据有限。方法：2019年至2022年期间，荷兰所有BRAF v600突变黑色素瘤和脑转移患者均接受恩可非尼/比尼美替尼治疗，数据来自全国范围的荷兰黑色素瘤治疗登记处。先前使用其他BRAF/MEK抑制剂治疗的患者被排除在外。我们分析了客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。多变量Cox回归确定了与生存率相关的因素。亚组分析包括无症状vs有症状脑转移和治疗方案（一线vs后一线）。结果共纳入190例患者。63 %的患者出现症状性脑转移。恩科非尼/比尼美替尼是64% %的患者的一线治疗，而36% %的患者先前接受过免疫治疗。总体而言，ORR为69.4% %，中位PFS为5.5个月（95 %CI 4.9-6.2），中位OS为11.9个月（95 %CI 10.0-15.7）。年龄≥ 70，ECOG PS≥ 2，症状性脑转移和LDH升高与较差的生存率显著相关。先前接受免疫治疗的患者的中位PFS为6.9个月（95 %CI 4.3-9.6）， OS为17.9个月（95 %CI 13.7-31.2），而treatment-naïve患者的中位PFS为4.9个月（95 %CI 4.3-5.5）和10.1个月（95 %CI 8.1-13.0）。无症状和有症状脑转移患者的中位PFS和OS分别为6.1个月（95 %CI 4.9-9.8）和20.5个月（95 %CI 14.0-NA），而5.3个月（95 %CI 4.9-6.3）和10.7个月（95 %CI 8.9-13.7）。结论恩科非尼/比尼美替尼在现实世界黑色素瘤伴脑转移患者中具有临床活性。他们的预后取决于症状性脑转移的存在、年龄、ECOG PS和LDH水平。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.