FDA Approves Once-Weekly Carfilzomib in Combination With Dexamethasone for Relapsed or Refractory Multiple Myeloma
Today, the U.S. Food and Drug Administration (FDA) approved a supplemental new drug application (sNDA) to expand the prescribing information for carfilzomib (Kyprolis) to include a once-weekly dosing option in combination with dexamethasone (once-weekly Kd70) for patients with relapsed or refractory multiple myeloma. The approval is based on data from the phase III ARROW trial, which demonstrated that carfilzomib administered once weekly at 70 mg/m2 with dexamethasone achieved superior progression-free survival and overall response rates with a comparable safety profile vs twice-weekly carfilzomib administered at a dose of 27 mg/m2 in combination with dexamethasone (twice-weekly Kd27). Carfilzomib is not approved for twice-weekly 27 mg/m2 administration in combination with dexamethasone alone.
The FDA reviewed the application under its Oncology Center of Excellence Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. The FDA approved the application just over 1 month after the final component of the application was submitted.
More About ARROW
ARROW included 478 patients with relapsed and refractory multiple myeloma who received at least two or three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent. Patients in the trial treated with once-weekly Kd70 achieved a statistically significant 3.7 month improvement in progression-free survival compared to the Kd27 twice-weekly regimen (median progression-free survival = 11.2 months for once-weekly Kd70 vs 7.6 months for twice-weekly Kd27; hazard ratio = 0.69, 95% confidence interval = 0.54–0.88; one-sided P = .0014).
The overall response rate in patients treated with once-weekly Kd70 was 62.9% vs 40.8% for those treated with twice-weekly Kd27 (P < .0001). In addition, 7.1% had complete responses or better in the once-weekly arm vs 1.7% in the twice-weekly arm in this refractory patient population.
The overall safety profiles of the two arms in ARROW were comparable, with no new safety risks identified in the once-weekly arm. Discontinuation rates due to adverse events were similar in the two arms. The most frequently reported treatment-emergent adverse events (≥ 20%) in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.
The trial was conducted at approximately 100 sites worldwide. The interim data were presented during at the 2018 ASCO Annual Meeting by Mateos et al (Abstract 8000) and simultaneously published by Moreau et al in The Lancet Oncology.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
