title: A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma.
abstract: Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m(2) intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m(2) for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response). Secondary endpoints included clinical benefit response rate (≥ minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. Overall response rate was 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238.
authors: John Theurer Cancer Center at Hackensack University, Hackensack, NJ 07601, USA. dsiegel@hackensackumc.org
authors: David S
authors: DS
authors: Siegel
authors: Thomas
authors: T
authors: Martin
authors: Michael
authors: M
authors: Wang
authors: Ravi
authors: R
authors: Vij
authors: Andrzej J
authors: AJ
authors: Jakubowiak
authors: Sagar
authors: S
authors: Lonial
authors: Suzanne
authors: S
authors: Trudel
authors: Vishal
authors: V
authors: Kukreti
authors: Nizar
authors: N
authors: Bahlis
authors: Melissa
authors: M
authors: Alsina
authors: Asher
authors: A
authors: Chanan-Khan
authors: Francis
authors: F
authors: Buadi
authors: Frederic J
authors: FJ
authors: Reu
authors: George
authors: G
authors: Somlo
authors: Jeffrey
authors: J
authors: Zonder
authors: Kevin
authors: K
authors: Song
authors: A Keith
authors: AK
authors: Stewart
authors: Edward
authors: E
authors: Stadtmauer
authors: Lori
authors: L
authors: Kunkel
authors: Sandra
authors: S
authors: Wear
authors: Alvin F
authors: AF
authors: Wong
authors: Robert Z
authors: RZ
authors: Orlowski
authors: Sundar
authors: S
authors: Jagannath
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D009842:Oligopeptides / Q000627:therapeutic use*; D010865:Pilot Projects; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D009842:Oligopeptides; C524865:carfilzomib