Abstract 5479
Background
Over 60% of patients (pts) with stage IV melanoma may develop brain metastases, resulting in a significantly increased morbidity and poor overall prognosis. Clinical data for melanoma brain metastases (MBM) treatments are limited, as controlled studies often exclude pts with untreated brain metastases.
Methods
We conducted a multicenter, retrospective case series investigation with consecutive pts with BRAF-mutant MBM who were treated with BRAF inhibitor encorafenib plus MEK inhibitor binimetinib to evaluate the antitumor response with this combination. Assessments included intracranial, extracranial & global objective response rates (ORRs; percentage of complete [CR] + partial [PR] responses) evaluated by modified RECIST version 1.1; clinical benefit rate (CBR; percentage of CR + PR + stable disease [SD] as best response); time to response, duration of response, and safety.
Results
A total of 17 pts with stage IV BRAF-mutant MBM who received encorafenib plus binimetinib in centers in the United States were included. Pts had received a median of 2 prior lines of treatment over a median of 520 days since their melanoma diagnosis (median of 55 days since diagnosis of MBM). Of the patients included, 82% had prior treatment with BRAF/MEK inhibitors. The intracranial ORR was 35% (with 3 CRs and 3 PRs) and CBR was 76%, with a median duration of response of 17 weeks. Eight pts with either stable disease or a response were still ongoing treatment at the time of this analysis. Among the 14 MBM pts with prior BRAF/MEK inhibitor treatment, the intracranial ORR was 21% and CBR was 71%. Similar outcomes were observed for extracranial and global responses. The safety profile for encorafenib plus binimetinib was similar to that observed in pts with melanoma without brain metastases.
Conclusions
Combination therapy with encorafenib plus binimetinib elicited intracranial activity in pts with BRAF-mutant MBM, including in pts previously treated with BRAF/MEK inhibitors. Further prospective studies are warranted. *K. Holbrook and J. Lutzky are co-first authors.
Clinical trial identification
Editorial acknowledgement
Editorial assistance was provided by JD Cox and Mayville Medical Communications, with funding from Array Biopharma.
Legal entity responsible for the study
Array BioPharma Inc.
Funding
Array BioPharma.
Disclosure
J. Lutzky: Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma; Advisory / Consultancy, Speaker Bureau / Expert testimony: Regeneron; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Bristol-Myers Squibb. A. Amin: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy: Merck; Speaker Bureau / Expert testimony: Regeneron. J.M. Davis: Speaker Bureau / Expert testimony: Exelixis Inc; Advisory / Consultancy: Array BioPharma. M.A. Davies: Advisory / Consultancy: Array BioPharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Vaccinex; Advisory / Consultancy: Syndax; Non-remunerated activity/ies: Nanostring. A. Diab: Advisory / Consultancy: Array BioPharma. I.C. Glitza: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Array BioPharma. R.N. Amaria: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Iovance. S. Patel: Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Cardinal Health; Advisory / Consultancy: Castle Biosciences; Research grant / Funding (institution): Deciphera; Advisory / Consultancy, DSMB: Immunocore; Advisory / Consultancy: Incyte; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Provectus; Advisory / Consultancy, Research grant / Funding (institution), DSMB: Reata. H.A. Tawbi: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Array BioPharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): GSK. All other authors have declared no conflicts of interest.
Resources from the same session
4596 - A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis (MBM) (POLARIS)
Presenter: Michael Davies
Session: Poster Display session 3
Resources:
Abstract
1891 - Continuation of annual screening mammograms and breast-cancer mortality in women over 70
Presenter: Xabier Garcia De Albeniz
Session: Poster Display session 3
Resources:
Abstract
5587 - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice
Presenter: Istvan Petak
Session: Poster Display session 3
Resources:
Abstract
4757 - Effectively using primary care givers in oncology care through capacity building, task sharing and techno-mentoring.
Presenter: Dinesh Pendharkar
Session: Poster Display session 3
Resources:
Abstract
4497 - A single institution review of capecitabine related acute admissions and cost analysis
Presenter: Gemma Dart
Session: Poster Display session 3
Resources:
Abstract
2187 - Health status of middle-aged and older cancer survivors in China: results from the China Health and Retirement Longitudinal Study (CHARLS)
Presenter: Jiarui Li
Session: Poster Display session 3
Resources:
Abstract
5101 - Crossed looks on lung cancer perception and knowledge from general public and physicians in France: results of a two-fold survey
Presenter: Céline Mascaux
Session: Poster Display session 3
Resources:
Abstract
4354 - Knowledge and perception of clinical trials (CTs) and attitude towards participation among Polish oncological patients - A pilot survey
Presenter: Artur Kotowski
Session: Poster Display session 3
Resources:
Abstract
3499 - Achieving best possible cancer treatment outcomes in care pathways through benchmarking; ABC-Benchmarking
Presenter: Anke Wind
Session: Poster Display session 3
Resources:
Abstract
2270 - Impact of 10-day Fulbright Specialist Program (FSP) and Project Pink Blue (PPB) Education Sessions on Medical Oncology knowledge among Doctors that treat cancer in Nigeria
Presenter: Mike Martin
Session: Poster Display session 3
Resources:
Abstract