LBA28CARFILZOMIB (K) VS LOW-DOSE CORTICOSTEROIDS AND OPTIONAL CYCLOPHOSPHAMIDE (CY) IN PATIENTS (PTS) WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA (RRMM): RESULTS FROM A PHASE 3 STUDY (FOCUS)

ABSTRACT Aim: To compare K with low-dose corticosteroids and optional Cy in RRMM (NCT01302392). Methods: Pts were randomized 1:1 to receive K or an active control of low-dose corticosteroids and optional Cy. Pts received K (10-min IV infusion) on Day (D) 1, 2, 8, 9, 15, 16 of a 28-D cycle (20 mg/m2 on D 1 and 2 of Cycle 1; 27 mg/m2 thereafter) or 84 mg of dexamethasone (or equivalent corticosteroid) with optional Cy (maximum 1400 mg) per 28-D cycle. The primary endpoint was overall survival (OS) with 80% power to detect a hazard ratio (HR) of 0.7 (median OS assumptions: K, 8.6 months [mo]; control: 6 mo). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR) and safety. Results: Data are presented for the K group followed by the control group. Between Sept 2010 and Oct 2012, 315 pts (278 from Europe) were randomized (K: 157 pts; control: 158 pts). Baseline characteristics were balanced between the groups. Median age was 65.0 yrs (range: 32–85). Pts received 5 (median) prior regimens in each group; median time since diagnosis was 6.0 yrs and 5.4 yrs. Median treatment duration was 16.3 weeks and 10.7 weeks; 92% of pts in the control group received Cy. Median relative dose intensity (actual dose/planned dose) was 99.9% in each group. The study did not meet the primary endpoint for OS (HR = 0.975; 95% confidence interval [CI]: 0.760–1.249; P = 0.4172). Median OS was 10.2 mo (95% CI: 8.4–14.4) and 10.0 mo (95% CI: 7.7–12.0). Median (range) follow-up for OS was 27.8 mo (0.1–42.5) and 29.8 mo (0.0–44.8). Median PFS was 3.7 mo (95% CI: 2.8–4.2) and 3.3 mo (95% CI: 2.2–5.2). The ORR was 19.1% (95% CI: 13.3–26.1) and 11.4% (95% CI: 6.9–17.4). Treatment discontinuation due to an adverse event (AE) occurred in 14.6% and 20.3% of pts; 10.2% and 12.4% of pts died on study due to an AE. Grade ≥3 treatment-emergent AEs (≥5%) included anemia (25.5% vs 30.7%), thrombocytopenia (24.2% vs 22.2%), neutropenia (7.6% vs 12.4%), acute renal failure (7.6% vs 3.3%), pneumonia (6.4% vs 12.4%), and renal failure (5.1% vs 1.3%). Conclusions: Median OS for single-agent K (10.2 mo) was similar to the active control arm (10 mo) in these heavily pretreated pts with RRMM. Disclosure: H. Ludwig: Research funding: Celgene, Janssen-Cilag, Mundipharma; Advisory Board: Celgene, Bristol-Meyers, Janssen-Cilag, Onyx; M.T. Petrucci: Consultancy and honoraria for Janssen-Cilag, Celgene, and Bristol-Myers Squibb; A. Palumbo: Consultancy -Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millenium, Onyx;Honoraria -Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millenium, Onyx; L. Rosinol: honoraria from Janssen and Celgene; A. Nagler: Research funding from Onyx; M.A. Dimopoulos: Honoraria from Onyx V. Maisnar: Consultancy - Celgene; Honoraria directly received from an entity - Celgene, Janssen, Amgen;Membership on an entity's board of directors, speakers bureau,or its advisory committees - Celgene K. Rajangam: employee of Onyx; J.F. San Miguel: He has participated in several compensated advisory boards for Millennium, Onyx, Celgene, Novartis, Janssen; R. Hajek: consultancy–Celgene,Merck; Honoraria - Celgene, Janssen, Merck. All other authors have declared no conflicts of interest.