A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)
Hájek R (1), Masszi T (2), Petrucci MT (3), Palumbo A (4), Rosiñol L (5), Nagler A (6), Yong KL (7), Oriol A (8), Minarik J (9), Pour L (1), Dimopoulos MA (10), Maisnar V (11), Rossi D (12), Kasparu H (13), Van Droogenbroeck J (14), Yehuda DB (15), Hardan I (16), Jenner M (17), Calbecka M 18, Dávid M (19), de la Rubia J (20), Drach J (21), Gasztonyi Z (22), Górnik S (23), Leleu X 24, Munder M (25), Offidani M (26), Zojer N (27), Rajangam K (28), Chang YL (28), San-Miguel JF (29), Ludwig H (30).
This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM).
Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles.
The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide.
Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172).
Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control.
Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.
CITATION Leukemia. 2016 Jul 15. doi: 10.1038/leu.2016.176