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
| Autor: | David S. Siegel, Sagar Lonial, Robert Z. Orlowski, Michael Wang, Michael Sebag, Alvin F. Wong, Lori Kunkel, Jonathan L. Kaufman, Nizar J. Bahlis, Andrzej Jakubowiak, Sandra Wear, Ravi Vij, Nashat Gabrail, Frederic J. Reu, Peter P. Lee, Melissa Alsina, Jeffrey Matous, Andrew R. Belch, Sundar Jagannath, David H. Vesole, A. Keith Stewart, Peter Rosen, Vishal Kukreti, Kevin T. McDonagh |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Time Factors Clinical Trials and Observations Immunology Antineoplastic Agents Biochemistry Gastroenterology Disease-Free Survival Bortezomib Cohort Studies chemistry.chemical_compound Recurrence Internal medicine medicine Clinical endpoint Humans Adverse effect Multiple myeloma Aged Demography Aged 80 and over business.industry Cell Biology Hematology Middle Aged medicine.disease Carfilzomib Boronic Acids Surgery Treatment Outcome chemistry Pyrazines Cohort Proteasome inhibitor Female business Multiple Myeloma Oligopeptides medicine.drug Cohort study |
| Zdroj: | Blood. 119(24) |
| ISSN: | 1528-0020 0053-0816 |
| Popis: | 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/m2 for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m2 for cycle 1 and then 27 mg/m2 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. |
| Databáze: | OpenAIRE |
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