Abstract 826P
Background
Patients (pts) with symptomatic melanoma brain metastases (MBM) have very poor prognosis. For BRAF mutated (mut) targeted therapy achieves high intracranial response rate (iRR) but intracranial progression free survival (iPFS) is usually short. With immunotherapy iRR can be long lasting in asymptomatic pts but are less frequent in symptomatic ones, especially if they need steroids GEM1802/EBRAIN (NCT03898908) evaluates iRR with encorafenib and binimetinib (EB) and explores if adding brain radiotherapy (RDT) could improve the iPFS in pts with both asymptomatic and symptomatic BRAF mut MBM. We present final results for symptomatic pts.
Methods
15 pts were treated with 2 months of EB at standard dose. If intracranial partial response (PR) or stable disease (SD), brain RDT (radiosurgery (SRS) or whole brain RDT (WBRT) was offered according to local guidelines followed by EB. For pts with complete response (CR) RDT could be spare and used in a later progressive disease (PD). iRR, iPFS, overall survival (OS) and QoL (QLQ-C30) were analyzed.
Results
Table summarizes pts´ basal characteristics. iRR after 2 months of EB was 73.3% (6.7% CR and 66.7% PR) with 26.7% SD and no PD. 20% pts received SRS & 46.7% WBRT after 1st evaluation. With a median follow up of 11.8 months (m) (Range: 3.4-23.1) median iPFS was 9.3 m (95% CI: 7.6-NR) with 73.3 & 23.3% of pts progression free at 6 & 12m respectively. Median OS was 18.4m (95% CI: 12.1-NR) with 93.3, 72.7 & 62.3% of pts alive at 6, 12 & 18m respectively. 20% of pts experienced G3-4 toxicity from EB and 6.7% from RDT. Global health status, pain and insomnia scales improved compared to baseline at week 16 (p=0.014, 0.028 and 0.045 respectively). Table: 826P
| Median age (range) | 49y (21-79) |
| Sex | 60% female |
| Brain Tumor Burden (target lesions), mean (95%CI) | 51.9 mm (32.9-70.9) |
| % | |
| >ULN LDH | 33.3 |
| Number of target BMs (1 vs 2-3 vs >3) | 33.3 - 46.7 - 20 |
| Extracranial disease | 93.3 |
| ECOG 0-1 | 86.6 |
| Basal steroids | 93.3 |
| Previous systemic treatment | 13.3 |
Conclusions
EB achieve a significant iRR in pts with symptomatic brain BRAF mut MBM and very bad prognosis factors (need for steroids and high intracranial tumor burden). Adding brain RDT is feasible and could help to improve the intracranial disease control provided by EB.
Clinical trial identification
NCT03898908.
Editorial acknowledgement
mFAR, the CRO of the trial, provided assistance in the writing of the abstract.
Legal entity responsible for the study
Spanish Melanoma Group (GEM).
Funding
Pierre Fabre.
Disclosure
I. Marquez-Rodas: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, Roche, GSK, AstraZeneca, Celgene, Regeneron, Sanofi, Merck Serono, Highligth Therapeutics, Bioline Rx, Sun Pharma; Financial Interests, Personal and Institutional, Invited Speaker, GEM1802 clinical trial: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, GEM1801 clinical study: Novartis, BMS, Roche, Pierre Fabre, Incyte, MSD; Financial Interests, Institutional, Invited Speaker, National coordinator of Spotlight 203 clinical trial: Highlight Therapeutics; Non-Financial Interests, Invited Speaker: Spanish Melanoma Group. A.M. Arance Fernandez: Financial Interests, Personal, Advisory Board, Consultant /Advisory/ Speaker / Travel, Accommodations, Expenses/: Pierre Fabre, Novartis, Roche, BMS, MSD, Merck, Sanofi; Financial Interests, Personal and Institutional, Other, Research Funding: Pierre Fabre, Novartis, MSD, BMS, Merck, Roche, Sanofi; Financial Interests, Institutional, Other, Research Funding: Amgem. M.A. Berciano Guerrero: Financial Interests, Personal, Invited Speaker: BMS, MSD, Pierre Fabre, Roche, Pfizer, Sanofi, Eisai, PharmaMar, Kyowa Kirin; Financial Interests, Personal, Advisory Board: BMS, MSD, Pierre Fabre, Roche, Pfizer, Sanofi, Eisai, PharmaMar. M. Gonzalez Cao: Financial Interests, Personal, Invited Speaker: BMS, Roche, MSD, Novartis, Pierre Fabre, AstraZeneca. P. Sanchez Mauriño: Financial Interests, Personal, Other: Novartis, BMS, Pierre Fabre, Sanofi, MSD. A. Alvarez: Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: PharmaMar. A. Berrocal: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Roche, Pierre Fabre, Merck. All other authors have declared no conflicts of interest.