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Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series.

Authors
  • Holbrook, Kourtney1
  • Lutzky, Jose2
  • Davies, Michael A1
  • Davis, Jessica Michaud3
  • Glitza, Isabella C1
  • Amaria, Rodabe N1
  • Diab, Adi1
  • Patel, Sapna P1
  • Amin, Asim3
  • Tawbi, Hussein1
  • 1 The University of Texas MD Anderson Cancer Center, Houston, Texas.
  • 2 Mount Sinai Comprehensive Cancer Center, Miami Beach, Florida.
  • 3 Levine Cancer Institute, Atrium Health, Charlotte, North Carolina.
Type
Published Article
Journal
Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2020
Volume
126
Issue
3
Pages
523–530
Identifiers
DOI: 10.1002/cncr.32547
PMID: 31658370
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Sixty percent of patients with stage IV melanoma may develop brain metastases, which result in significantly increased morbidity and a poor overall prognosis. Phase 3 studies of melanoma usually exclude patients with untreated brain metastases; therefore, clinical data for intracranial responses to treatments are limited. A multicenter, retrospective case series investigation of consecutive BRAF-mutant patients with melanoma brain metastases (MBMs) treated with a combination of BRAF inhibitor encorafenib and MEK inhibitor binimetinib was conducted to evaluate the antitumor response. Assessments included the intracranial, extracranial, and global objective response rates (according to the modified Response Evaluation Criteria in Solid Tumors, version 1.1); the clinical benefit rate; the time to response; the duration of response; and safety. A total of 24 patients with stage IV BRAF-mutant MBMs treated with encorafenib plus binimetinib in 3 centers in the United States were included. Patients had received a median of 2.5 prior lines of treatment, and 88% had prior treatment with BRAF/MEK inhibitors. The intracranial objective response rate was 33%, and the clinical benefit rate was 63%. The median time to a response was 6 weeks, and the median duration of response was 22 weeks. Among the 21 patients with MBMs and prior BRAF/MEK inhibitor treatment, the intracranial objective response rate was 24%, and the clinical benefit rate was 57%. Similar outcomes were observed for extracranial and global responses. The safety profile for encorafenib plus binimetinib was similar to that observed in patients with melanoma without brain metastases. Combination therapy with encorafenib plus binimetinib elicited intracranial activity in patients with BRAF-mutant MBMs, including patients previously treated with BRAF/MEK inhibitors. Further prospective studies are warranted and ongoing. © 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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