Once- vs Twice-Weekly Carfilzomib in Relapsed or Refractory Multiple Myeloma
An interim analysis of the phase III ARROW trial reported in The Lancet Oncology by Moreau et al indicated that a higher-dose once-weekly schedule of carfilzomib was associated with prolonged progression-free survival vs a twice-weekly schedule in patients with relapsed or refractory multiple myeloma.
Study Details
In the open-label trial, 478 patients from 118 sites in North America, Europe, and Asia were randomly assigned between September 2015 and August 2016 to receive carfilzomib at 70 mg/m2 once weekly (n = 240) or 27 mg/m2 twice weekly in 28-day cycles. Patients had to have received two or three prior treatments, including a proteasome inhibitor and immunomodulatory agent. All patients received dexamethasone at 40 mg on days 1, 8, and 15 in all cycles and on day 22 in cycles 1 to 9.
Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival in the intention-to-treat population.
The median follow-up for progression-free survival was 12.0 months. The median progression-free survival was 11.2 months in the once-weekly group vs 7.6 months in the twice-weekly group (hazard ratio [HR] = 0.69, P = .0029). Hazard ratios favored once-weekly treatment in all examined subgroups except for the subgroup with standard-risk cytogenetics (HR = 1.00).
The overall response rates were 62.9% vs 40.8% (odds ratio = 2.49, P < .0001). Overall survival data were not mature at the time of analysis, with a median follow-up of approximately 13 months; 12-month overall survival rates were 76.6% vs 71.9%.
Adverse Events
Grade 3 or worse adverse events occurred in 68% vs 62% of patients, with the most common being anemia (18% vs 18%), pneumonia (10% vs 7%), and thrombocytopenia (7% vs 7%). Grade 3 or worse cardiac failure occurred in 3% vs 4% of patients. Treatment-related deaths occurred in 5 patients in the once-weekly group (due to sepsis, death—not otherwise specified, acute lung injury, acute respiratory distress syndrome, and tumor-lysis syndrome) and 2 patents in the twice-weekly group (due to plasma cell myeloma and congestive heart failure).
The investigators concluded, “Once weekly carfilzomib at 70 mg/m2 significantly prolonged progression-free survival vs the twice weekly schedule. Overall safety was comparable between the groups. Once weekly carfilzomib appears safe and more effective with a convenient dosing regimen vs the twice weekly schedule for the treatment of patients with relapsed and refractory multiple myeloma.”
The study was funded by Amgen, Inc.
Philippe Moreau, MD, of the Hematology Department, University Hospital Hotel-Dieu, Nantes, is the corresponding author for The Lancet Oncology article.
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