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
4868 - Evaluation of markers associated with efficacy of abiraterone acetate plus prednisone (AAP) in patients (pts) with castration-sensitive prostate cancer (mCSPC) from the LATITUDE study
Presenter: Kim Chi
Session: Poster Display session 3
Resources:
Abstract
4837 - LRP2, a potential new biomarker for Chinese younger aged intrahepatic cholangiocarcinoma patients
Presenter: Xiaoliang Shi
Session: Poster Display session 3
Resources:
Abstract
1286 - Reanalysis of the efficacy of molecular targeted agents (MTAs) given in the randomized trial SHIVA01 according to the ESMO ESCAT scale of actionability
Presenter: Aurelie Moreira
Session: Poster Display session 3
Resources:
Abstract
2736 - Comparison of Platforms for Determining Tumor Mutational Burden (TMB) From Blood Samples in Patients With Non-Small Cell Lung Cancer (NSCLC)
Presenter: Jonathan Baden
Session: Poster Display session 3
Resources:
Abstract
5045 - Comprehensive Pan-Cancer analysis of somatic mutations in drug transporters to reveal acquired and intrinsic drug resistance in 3149 metastatic cancer patients
Presenter: Sander Bins
Session: Poster Display session 3
Resources:
Abstract
4577 - Pan-Cancer Genomic Landscape of the Cyclin D1/FGF3,4,19 (11q13) Amplicon Including Associations with HPV Status, and ESR1 and AR Alterations
Presenter: Jennifer Johnson
Session: Poster Display session 3
Resources:
Abstract
5366 - Co-occurrence of NTRK fusions with other genomic biomarkers in cancer patients
Presenter: Xiaolong Jiao
Session: Poster Display session 3
Resources:
Abstract
4084 - Prospective comparative study of next-generation sequencing on fine needle aspirations versus core needle biopsies in cancer patients included in SHIVA02 trial
Presenter: Julien Masliah-Planchon
Session: Poster Display session 3
Resources:
Abstract
6017 - First national External Quality Assessement for the interpretation of somatic variants: assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France
Presenter: Etienne Rouleau
Session: Poster Display session 3
Resources:
Abstract
2283 - Prospective testing of circulating tumor DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology
Presenter: Andjelija Bujak
Session: Poster Display session 3
Resources:
Abstract