Vemurafenib in patients with BRAF^V600 mutation-positive melanoma with symptomatic brain metastases: Final results of an open-label pilot study

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• 作者：Reinhard Dummer ; Simone M. Goldinger ; Christian P. Turtschi ; Nina B. Eggmann ; Olivier Michielin ; Lada Mitchell ; Luisa Veronese ; Paul Ren茅 Hilfiker ; Lea Felderer ; Jeannine D. Rinderknecht
• 关键词：BRAF mutation ; BRAF inhibitor ; Vemurafenib ; Advanced melanoma ; Symptomatic brain metastases ; Safety ; Tumour regression
• 刊名：European Journal of Cancer
• 出版年：February, 2014
• 年：2014
• 卷：50
• 期：3
• 页码：611-621
• 全文大小：702 K

文摘

Background & Aim

Brain metastases are frequent in patients with metastatic melanoma, indicating poor prognosis. We investigated the BRAF kinase inhibitor vemurafenib in patients with advanced melanoma with symptomatic brain metastases.

Methods

This open-label trial assessed vemurafenib (960 mg twice a day) in patients with BRAF^V600 mutation-positive metastatic melanoma with non-resectable, previously treated brain metastases. The primary end-point was safety. Secondary end-points included best overall response rate, and progression-free and overall survival.

Results

Twenty-four patients received vemurafenib for a median treatment duration of 3.8 (0.1-11.3) months. The majority of discontinuations were due to disease progression (n = 22). Twenty-three of 24 patients reported at least one adverse event (AE). Grade 3 AEs were reported in four (17%; 95% confidence interval [CI], 4.7-37.4%) patients and included cutaneous squamous cell carcinoma in four patients. Median progression-free survival was 3.9 (95% CI, 3.0-5.5) months, and median survival was 5.3 (95% CI, 3.9-6.6) months. An overall partial response (PR) at both intracranial and extracranial sites was achieved in 10 of 24 (42%; 95% CI, 22.1-63.4) evaluable patients, with stable disease in nine (38%; 95% CI, 18.8-59.4) patients. Of 19 patients with measurable intracranial disease, seven (37%) achieved >30% intracranial tumour regression, and three (16%; 95% CI, 3.4-39.6%) achieved a confirmed PR. Other signs of improvement included reduced need for corticosteroids and enhanced performance status.

Conclusions

Vemurafenib can be safely used in patients with advanced symptomatic melanoma that has metastasised to the brain and can result in meaningful tumour regression.