Abstract 1154TiP
Background
In patients with MM, brain mets are an indication of poor prognosis, with short OS, PFS and neurological deterioration. Median OS from diagnosis of brain mets is in the range of 17–22 weeks (w), suggesting a crucial need for treatments that can control central nervous system (CNS) progression. Until recently, the management of MM brain mets has included surgical resection, stereotactic radiosurgery, whole-brain radiation therapy, and/or cytotoxic chemotherapy, without a clear change in the natural history of the disease. New drug therapies based on combined BRAF+MEK inhibition for pts BRAF V600 mutant and immunotherapies such as CTLA-4 inhibitors and PD-1 inhibitors, have shown promising results in the setting of MM, leading to median OS of 14-23 months (m). We hypothesize that the early diagnosis of brain mets will improve the symptomatic brain mets free survival (SBMFS) in pts with previously untreated, unresectable or MM by guiding effective treatment options.
Trial design
This is a randomized, open-label, multi-center, phase II study to assess the impact of early detection of asymptomatic brain mets vs standard follow-up on SBMFS in patients with previously untreated, unresectable or MM. A total of 122 pts will be randomized 1:1 to (i) experimental group: serial brain magnetic resonance imaging (MRI); or (ii) control group: standard follow-up. The stratification factors used for randomization are: LDH (normal vs. above upper normal limit); and BRAF V600 (mutated vs. wild-type). Pts in experimental group will undergo brain MRI scans every 16 w or sooner if the patient presents neurological symptoms. Patients in control group will receive neurological examination as per standard of care and CNS imaging will be performed at the time of neurological symptoms/signs. The primary endpoint is SBMFS. The study has 80% power to detect an improvement of 6m in median SBMFS using 80% confidence interval. The follow-up visits in both groups will be every 16 w (+/- 7 d) with a maximum follow-up of 36 m for OS. Recruitment period was estimated in 18 m, with total study duration of 42 m.
Clinical trial identification
CA209-7J3/ VHIO19pr001.
Editorial acknowledgement
Legal entity responsible for the study
VHIO; Vall d’Hebron Insitute of Oncology.
Funding
Bristol-Myers Squibb.
Disclosure
E. Munoz Couselo: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre-Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck. G. Villacampa Javierre: Speaker Bureau/Expert testimony: Merck Sharp; Speaker Bureau/Expert testimony: Dohme. All other authors have declared no conflicts of interest.