title: Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR.
abstract: The randomized phase 3 study ENDEAVOR demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (MM). We conducted a preplanned subgroup analysis of ENDEAVOR to evaluate Kd vs Vd by cytogenetic risk. Of 785 patients with known cytogenetics, 210 (27%) had high-risk cytogenetics (Kd, n=97 (25%); Vd, n=113 (28%)) and 575 (73%) had standard-risk cytogenetics (Kd, n=284 (75%); Vd, n=291 (72%)). Median PFS in the high-risk group was 8.8 months for Kd vs 6.0 months for Vd (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.45-0.92; P=0.0075). Median PFS in the standard-risk group was not estimable for Kd vs 10.2 months for Vd (HR, 0.44; 95% CI, 0.33-0.58; P<0.0001). Overall response rates were 72.2% (Kd) vs 58.4% (Vd) in the high-risk group and 79.2% (Kd) vs 66.0% (Vd) in the standard-risk group. In the high-risk group, 15.5% (Kd) vs 4.4% (Vd) achieved a complete response (CR) or better. In the standard-risk group, 13.0% (Kd) vs 7.9% (Vd) achieved ⩾CR. This preplanned subgroup analysis found that Kd was superior to Vd in relapsed or refractory MM, regardless of cytogenetic risk.
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore.|Department of Haematology-Oncology, Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: W-J
authors.initials: WJ
authors.lastname: Chng
authors.affiliation: Department of Internal Medicine, Heidelberg Medical University, Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Department of Haematology, University of Nantes, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Department of Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Joshua
authors.affiliation: Department of Oncology, University of Torino, Torino, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Department of Haematology, CHRU Lille Hôpital Claude Huriez, Lille, France.
authors.forename: T
authors.initials: T
authors.lastname: Facon
authors.affiliation: Department of Medicine, Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: Myeloma Group, University Hospital Brno, Brno, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Pour
authors.affiliation: Multiple Myeloma Center, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Niesvizky
authors.affiliation: Department of Clinical Haematology, Institut Català d'Oncologia, Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Department of Haematology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rosiñol
authors.affiliation: Hematological Department, First Republican Clinical Hospital of Udmurtia, Izhevsk, Russia.
authors.forename: A
authors.initials: A
authors.lastname: Suvorov
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Department of Hematooncology, University Hospital Olomouc, Olomouc, Czech Republic.
authors.forename: T
authors.initials: T
authors.lastname: Pika
authors.affiliation: Myeloma Clinic, Universitatsklinikum Tubingen, Tubingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Weisel
authors.affiliation: Haematooncology Clinic, University Multiprofile Hospital for Active Treatment 'Sveti Georgi' and Medical University, Plovdiv, Bulgaria.
authors.forename: V
authors.initials: V
authors.lastname: Goranova-Marinova
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Gillenwater
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Mohamed
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Feng
authors.affiliation: Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Haematooncology, University Hospital Ostrava, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
authors.forename: R
authors.initials: R
authors.lastname: Hájek
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D000069286:Bortezomib / Q000008:administration & dosage; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D009842:Oligopeptides; D000069286:Bortezomib; C524865:carfilzomib; D003907:Dexamethasone