title: A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS).
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/m2on days 1 and 2 of cycle 1; 27 mg/m2thereafter) 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.
authors.affiliation: University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
authors.forename: R
authors.initials: R
authors.lastname: Hájek
authors.affiliation: St István and St László Hospital of Budapest, Budapest, Hungary.
authors.forename: T
authors.initials: T
authors.lastname: Masszi
authors.affiliation: Sapienza University of Rome, Rome, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Petrucci
authors.affiliation: University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rosiñol
authors.affiliation: Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Nagler
authors.affiliation: University College London Cancer Institute, London, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Yong
authors.affiliation: Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Oriol
authors.affiliation: University Hospital Olomouc and Medical Faculty of Palacky, University Olomouc, Olomouc, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Minarik
authors.affiliation: University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Pour
authors.affiliation: National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Charles University Teaching Hospital, Hradec Králové, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Maisnar
authors.affiliation: Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Hospital Elisabethinen Linz, Linz, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Kasparu
authors.affiliation: AZ Sint-Jan, Brugge, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Van Droogenbroeck
authors.affiliation: Hadassah Medical Center, Jerusalem, Israel.
authors.forename: D B
authors.initials: DB
authors.lastname: Yehuda
authors.affiliation: Meir Medical Center, Kfar-Saba, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Hardan
authors.affiliation: Southampton General Hospital, Hampshire, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jenner
authors.affiliation: Nicolaus Copernicus Hospital, Toruń, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Calbecka
authors.affiliation: University of Pécs, Pécs, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Dávid
authors.affiliation: University Hospital La Fe and Universidad Católica de València 'San Vicente Mártir', València, Spain.
authors.forename: J
authors.initials: J
authors.lastname: de la Rubia
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Drach
authors.affiliation: Petz Aladár Megyei Oktató Kórház, Vasvári Pál, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Gasztonyi
authors.affiliation: Zamojski Szpital Niepubliczny, Zamosc, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Górnik
authors.affiliation: Hopital Huriez, CHRU, Lille, France.
authors.forename: X
authors.initials: X
authors.lastname: Leleu
authors.affiliation: University Medicine Mainz, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Munder
authors.affiliation: Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Offidani
authors.affiliation: Center for Oncology, Hematology with Outpatient Department and Palliative Care, Wilhelminenspital, Vienna, Austria.
authors.forename: N
authors.initials: N
authors.lastname: Zojer
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Rajangam
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Chang
authors.affiliation: Clínica Universidad de Navarra-CIMA-IDISNA, Navarra, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: San-Miguel
authors.affiliation: Wilhelminen Cancer Research Institute, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Ludwig
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009503:Neutropenia / Q000139:chemically induced; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000305:Adrenal Cortex Hormones; D009842:Oligopeptides; C524865:carfilzomib; D003520:Cyclophosphamide