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FDA Actions & Updates

The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.

Tuesday, October 2, 2018

Carfilzomib Once-Weekly Regimen With Dexamethasone Approved for R/R Multiple Myeloma

The FDA has approved the supplemental New Drug Application (sNDA) to expand the Prescribing Information for carfilzomib 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 A.R.R.O.W. trial (RAndomized, Open-label, Phase III Study in Subjects with Relapsed and Refractory Multiple Myeloma Receiving Carfilzomib in Combination with Dexamethasone, Comparing Once-Weekly versus Twice-weekly Carfilzomib Dosing), which demonstrated that carfilzomib administered once-weekly at 70 mg/m2with dexamethasone achieved superior progression-free survival (PFS) and overall response rates (ORR), with a comparable safety profile, versus 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 in just over one month after the final component of the application was submitted.

"While great progress has been made in the last decade, multiple myeloma remains an incurable disease characterized by a recurring pattern of remission and relapse, and it is important that patients have treatment options that meet their individual needs," said David S. Siegel, MD, PhD, Chief of the Division of Multiple Myeloma at John Theurer Cancer Center at Hackensack University Medical Center. "The availability of a more convenient once-weekly dosing regimen, with superior efficacy, comparable safety, and longer duration of therapy versus the twice-weekly regimen studied in the trial could allow patients to spend more time outside of the infusion center."

A.R.R.O.W. 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 PFS compared to the Kd27 twice-weekly regimen (median PFS 11.2 months for once-weekly Kd70 versus 7.6 months for twice-weekly Kd27; HR=0.69; 95 percent CI: 0.54-0.88; one-sided p=0.0014).The ORR in patients treated with once-weekly Kd70 was 62.9 percent versus 40.8 percent for those treated with twice-weekly Kd27 (p<0.0001). In addition, 7.1 percent had complete responses or better in the once-weekly arm versus 1.7 percent in the twice-weekly arm in this refractory patient population.

The overall safety profiles of the two arms in A.R.R.O.W. 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 (greater than or equal to 20%) in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.

The interim data were presented during an oral session at the 54th ASCO Annual Meeting and simultaneously published in The Lancet Oncology (2018;19(7):953-964).