Estimated median overall survival (OS) in patients (pts) with brain metastases (BM) ranges between 1.8-10.5 months (mo). Ipilimumab (IPI) has shown activity against mel-BM. Radiation (RT) might be synergistic to anti-CTLA-4 blockade through an ‘abscopal’ effect.
Open label single stage multicenter phase 2 study, assuming a historical 20% 1-year survival rate (1y SR) with RT. Target sample size: 56 evaluable pts. Target 1y SR: 35% (α= 0.05, ß= 0.2). Objectives: Primary: 1y SR; Secondary: progression free survival (PFS); OS; objective response rate (mWHO); safety and feasibility. Treatment: IPI 3 mg/Kg iv q 3 weeks (4 cycles); whole brain RT (WBRT) 30 Gy in 10 fractions (or equivalent), started between C1 and C2. Main eligibility: First episode of BM in mel pts; Karnofsky PS > 70%; Barthel Index > 10; RTOG-RPA class 2; measurable disease; LDH 16 mg/d (or equivalent).
This is a preliminary analysis after recruiting 43/56 pts (Apr 2014 - Mar 2016). Demographical characteristics are shown in the table.
|Age (median (range))||65 (37-83)|
|Gender (male; female)||25; 18|
|Karnofsky PS(100-90; 70-80)||33; 8|
|Barthel Index (>15; 10-15)||35; 2|
|BRAF mutation||33% (11/33)|
|Previous lines (0; 1; >1)||22; 14; 7|
|Previous BRAF/MEK inh||9.3% (4/43)|
|Brain mets (single; multiple; NA)||8; 29; 6|
|Corticosteroids at baseline/C1||32.4%|
Concomitant IPI + WBRT is feasible. There were no unexpected safety issues. Despite the frequent need for costicosteroids at baseline, interim 1y SR is 31.4%. The trial is ongoing. Updated results will be presented.
Clinical trial identification
Legal entity responsible for the study
GEM (Grupo Español de Melanoma / Melanoma Spanish Group)
J.A. Lopez Martin: BMS: research grant, Advisory Board MSD: research grant, advisory board Roche: research grant Novartis: research grant. I. Marquez Rodas: Advisory role: BMS honoraria and travel accomodation: BMS. S. Martin-Algarra: BMS: Advisory Board, paid lectures. All other authors have declared no conflicts of interest.