title: An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma.
abstract: Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomib-naive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m(2) for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m(2) for cycle 1 and then 27 mg/m(2) for all subsequent cycles. The primary end point was an overall response rate (≥ partial response) of 42.4% in Cohort 1 and 52.2% in Cohort 2. The clinical benefit response (overall response rate + minimal response) was 59.3% and 64.2% in Cohorts 1 and 2, respectively. Median duration of response was 13.1 months and not reached, and median time to progression was 8.3 months and not reached, respectively. The most common treatment-emergent adverse events were fatigue (62.0%) and nausea (48.8%). Single-agent carfilzomib elicited a low incidence of peripheral neuropathy-17.1% overall (1 grade 3; no grade 4)-in these pretreated bortezomib-naive patients. The results of the present study support the use of carfilzomib in R/R MM patients. This trial is registered at www.clinicaltrials.gov as NCT00530816.
authors.affiliation: Washington University School of Medicine, St Louis, MO 63110, USA. rvij@im.wustl.edu
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Kaufman
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Jakubowiak
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: Kevin T
authors.initials: KT
authors.lastname: McDonagh
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Nizar J
authors.initials: NJ
authors.lastname: Bahlis
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Reu
authors.forename: Nashat Y
authors.initials: NY
authors.lastname: Gabrail
authors.forename: Andrew
authors.initials: A
authors.lastname: Belch
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Matous
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.forename: Peter
authors.initials: P
authors.lastname: Rosen
authors.forename: Michael
authors.initials: M
authors.lastname: Sebag
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
authors.forename: Lori A
authors.initials: LA
authors.lastname: Kunkel
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Wear
authors.forename: Alvin F
authors.initials: AF
authors.lastname: Wong
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D015331:Cohort Studies; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009842:Oligopeptides; D011719:Pyrazines; D000069286:Bortezomib; C524865:carfilzomib