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Clinical Trial
. 2017 Jan;31(1):107-114.
doi: 10.1038/leu.2016.176. Epub 2016 Jun 24.

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

R Hájek  1 , T Masszi  2 , M T Petrucci  3 , A Palumbo  4 , L Rosiñol  5 , A Nagler  6 , K L Yong  7 , A Oriol  8 , J Minarik  9 , L Pour  1 , M A Dimopoulos  10 , V Maisnar  11 , D Rossi  12 , H Kasparu  13 , J Van Droogenbroeck  14 , D B Yehuda  15 , I Hardan  16 , M Jenner  17 , M Calbecka  18 , M Dávid  19 , J de la Rubia  20 , J Drach  21 , Z Gasztonyi  22 , S Górnik  23 , X Leleu  24 , M Munder  25 , M Offidani  26 , N Zojer  27 , K Rajangam  28 , Y-L Chang  28 , J F San-Miguel  29 , H Ludwig  30
Affiliations
Clinical Trial

A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

R Hájek et al. Leukemia. 2017 Jan.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01302392.

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Conflict of interest statement

Dr Hájek reports funding from Celgene, Janssen and Merck outside of the submitted work; Dr Masszi has nothing to disclose; Dr Petrucci reports receiving personal fees from Janssen-Cilag, Celgene, and BMS outside the submitted work; Dr Palumbo reports receiving personal fees from Amgen, Bristol-Myers Squibb, Genmab A/S, Janssen-Cilag, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Sanofi Aventis, Celgene and Array BioPharma outside the submitted work; Dr Rosiñol reports personal fees from Onyx during the conduct of the study, and personal fees from Janssen, and Celgene outside the submitted work; Dr Nagler reports funding from Onyx outside the submitted work; Dr Yong has nothing to disclose; Dr Oriol reports other from Celgene, Jansen and Novartis outside the submitted work; Dr Minarik has nothing to disclose; Dr Pour has nothing to disclose; Dr Dimopoulos reports personal fees from Onyx and Celgene outside the submitted work; Dr Maisnar reports funding from Celgene, Janssen, and Amgen outside the submitted work; Dr Rossi has nothing to disclose; Dr Kasparu has nothing to disclose; Dr Droogenbroeck has nothing to disclose; Dr Ben-Yehuda has nothing to disclose; Dr Hardan has nothing to disclose; Dr Jenner received honoraria from Amgen/Onyx outside the submitted work; Dr Calbecka has nothing to disclose; Dr David has nothing to disclose; Dr de la Rubia has nothing to disclose; Dr Drach has nothing to disclose; Dr Gasztonyi has nothing to disclose; Dr Górnik has nothing to disclose; Dr Leleu reports funding from Celgene, Janssen, Leopharma, Amgen, Novartis, and Sanofi outside the submitted work; Dr Munder has nothing to disclose; Dr Offidani reports other from Celgene, Janssen, Amgen, Novartis, and Mundipharma outside the submitted work; Dr Zojer received honoraria from Janssen-Cilag and Mundipharma; Dr Chang is employed by, and owns stock in, Onyx; Dr Rajangam is employed by, and owns stock in, Onyx; Dr San Miguel reports funding from Millennium, Celgene, Novartis, Onyx, Janssen, BMS, and MSD outside the submitted work; and Dr Ludwig reports grants from Takeda, personal fees from Janssen-Cilag, Celgene, Bristol Meyers, Amgen and Onyx outside the submitted work.

Figures

Figure 1
Figure 1
Random assignment and follow-up.
Figure 2
Figure 2
Kaplan−Meier estimates of (a) OS and (b) PFS.
See this image and copyright information in PMC

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