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Leukemia. 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).

Author information

1
University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
2
St István and St László Hospital of Budapest, Budapest, Hungary.
3
Sapienza University of Rome, Rome, Italy.
4
University of Torino, Torino, Italy.
5
Hospital Clínic de Barcelona, Barcelona, Spain.
6
Chaim Sheba Medical Center, Tel Hashomer, Israel.
7
University College London Cancer Institute, London, UK.
8
Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain.
9
University Hospital Olomouc and Medical Faculty of Palacky, University Olomouc, Olomouc, Czech Republic.
10
National and Kapodistrian University of Athens, Athens, Greece.
11
Charles University Teaching Hospital, Hradec Králové, Czech Republic.
12
Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
13
Hospital Elisabethinen Linz, Linz, Austria.
14
AZ Sint-Jan, Brugge, Belgium.
15
Hadassah Medical Center, Jerusalem, Israel.
16
Meir Medical Center, Kfar-Saba, Israel.
17
Southampton General Hospital, Hampshire, UK.
18
Nicolaus Copernicus Hospital, Toruń, Poland.
19
University of Pécs, Pécs, Hungary.
20
University Hospital La Fe and Universidad Católica de València 'San Vicente Mártir', València, Spain.
21
Medical University of Vienna, Vienna, Austria.
22
Petz Aladár Megyei Oktató Kórház, Vasvári Pál, Hungary.
23
Zamojski Szpital Niepubliczny, Zamosc, Poland.
24
Hopital Huriez, CHRU, Lille, France.
25
University Medicine Mainz, Mainz, Germany.
26
Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy.
27
Center for Oncology, Hematology with Outpatient Department and Palliative Care, Wilhelminenspital, Vienna, Austria.
28
Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA.
29
Clínica Universidad de Navarra-CIMA-IDISNA, Navarra, Spain.
30
Wilhelminen Cancer Research Institute, Vienna, Austria.

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.

PMID:
27416912
PMCID:
PMC5220126
DOI:
10.1038/leu.2016.176
[Indexed for MEDLINE]
Free PMC Article

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.

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