FDA Approves Once-Weekly Carfilzomib With Dexamethasone in Resistant Multiple Myeloma
Posted: Tuesday, October 2, 2018
On October 1, 2018, the U.S. Food and Drug Administration (FDA) expanded the prescribing information for carfilzomib (Kyprolis) to include a once-weekly dosing option in combination with dexamethasone for patients with relapsed or refractory multiple myeloma.
The approval is based on data from the phase III ARROW trial (ClinicalTrials.gov identifier NCT02412878), 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 compared with 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 ARROW trial included 478 patients with relapsed and refractory multiple myeloma who received at least 2 or 3 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 with the twice-weekly Kd27 regimen. The overall response rate in patients treated with once-weekly Kd70 was 62.9% versus 40.8% for those treated with twice-weekly Kd27. In addition, 7.1% had complete responses or better in the once-weekly arm versus 1.7% in the twice-weekly arm in this refractory patient population.
The overall safety profiles of the two arms in this trial were comparable, with no new safety risks identified in the once-weekly arm. Treatment 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 interim data were presented at the 2018 American Society of Clinical Oncology Annual Meeting by Mateos et al (Abstract 8000), and simultaneously published in The Lancet Oncology, and covered in JNCCN 360.
