title: U.s. Food and Drug Administration approval: carfilzomib for the treatment of multiple myeloma.
abstract: The U.S. Food and Drug Administration (FDA) review leading to accelerated approval of carfilzomib is described. A single-arm trial enrolled 266 patients with multiple myeloma refractory to the most recent therapy who had received prior treatment with bortezomib and an immunomodulatory agent (IMID). Patients received carfilzomib by intravenous infusion over 2 to 10 minutes at a dose of 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 of the 28 days of cycle 1, and at a dose of 27 mg/m2 on the same schedule in cycle 2 and subsequent cycles. The primary efficacy endpoint was overall response rate (ORR) as determined by an independent review committee using International Myeloma Working Group Uniform Response Criteria. The safety of carfilzomib was evaluated in 526 patients with multiple myeloma treated with various dosing regimens. The ORR was 23%. The median duration of response was 7.8 months. The most common adverse reactions associated with carfilzomib infusion were fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and fever. The most common serious adverse events were pneumonia, acute renal failure, fever, and congestive heart failure. Infusion reactions to carfilzomib could be reduced by pretreatment with dexamethasone and intravenous fluids. On July 20, 2012, the FDA granted accelerated approval of carfilzomib for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an IMID and who have shown disease progression while on therapy or within 60 days of completion of the last therapy.
authors.affiliation: Office of Hematology and Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, USA. Thomas.Herndon@fda.hhs.gov
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Herndon
authors.forename: Albert
authors.initials: A
authors.lastname: Deisseroth
authors.forename: Edvardas
authors.initials: E
authors.lastname: Kaminskas
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kane
authors.forename: Kallappa M
authors.initials: KM
authors.lastname: Koti
authors.forename: Mark D
authors.initials: MD
authors.lastname: Rothmann
authors.forename: Bahru
authors.initials: B
authors.lastname: Habtemariam
authors.forename: Julie
authors.initials: J
authors.lastname: Bullock
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Bray
authors.forename: Jessica
authors.initials: J
authors.lastname: Hawes
authors.forename: Todd R
authors.initials: TR
authors.lastname: Palmby
authors.forename: Josephine
authors.initials: J
authors.lastname: Jee
authors.forename: William
authors.initials: W
authors.lastname: Adams
authors.forename: Houda
authors.initials: H
authors.lastname: Mahayni
authors.forename: Janice
authors.initials: J
authors.lastname: Brown
authors.forename: Angelica
authors.initials: A
authors.lastname: Dorantes
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Ann T
authors.initials: AT
authors.lastname: Farrell
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D017277:Drug Approval; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D009842:Oligopeptides; D061988:Proteasome Inhibitors; C524865:carfilzomib