©ASCO/Michael R. Schmidt
Attendees at ASCO 2018
CHICAGO—A once-weekly regimen of carfilzomib plus dexamethasone shows a favorable benefit-risk profile for patients with relapsed or refractory (R/R) multiple myeloma (MM), according to a new study.
“The more convenient dosing schedule can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” said investigator Maria-Victoria Mateos, MD, of the Hospital Clinico Universitario de Salamanca-IBSAL in Salamanca, Spain.
Dr Mateos presented results of the randomized, phase 3 study (abstract 8000) at the 2018 ASCO Annual Meeting. The results were also published in The Lancet.
Twice-weekly carfilzomib at 27 mg/m2 is approved as a single agent and in combination with lenalidomide or dexamethasone for the treatment of relapsed/refractory MM.
To develop a more convenient carfilzomib regimen, once-weekly carfilzomib plus dexamethasone was assessed in the phase 1/2 CHAMPION-1 study, showing good response rates (77%) and a median PFS of 12.6 months.
At ASCO, Dr Mateos presented the results from the pre-planned interim analysis of the phase 3 ARROW study (NCT02412878), comparing the two-drug regimen once-weekly vs twice-weekly.
Study design
The 478 patients, median age 66 years, had 2 to 3 prior therapies and prior exposure to a proteasome inhibitor and an immunomodulatory agent. Baseline characteristics were generally balanced, she said.
Investigators randomized patients to receive either once- or twice-weekly carfilzomib plus dexamethasone.
The once-weekly group received carfilzomib 20 mg/m2 intravenously on day 1 of cycle 1 and 70 mg/m2 on days 1, 8, and 15 of all subsequent cycles.
The twice-weekly group received the same carfilzomib dose on day 1, cycle 1 and 27 mg/m2 on days 8, 9, 15, and 16 thereafter. All patients received dexamethasone at 40 mg on days 1, 8, 15 (all cycles), and day 22 (cycles 1–9 only).
The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate, overall survival, safety, and pharmacokinetics.
Results
The study met the primary endpoint of PFS, with a median PFS for the once-weekly dose of 11.2 months and 7.6 months for the twice-weekly dose.
In addition, “patients who received once-weekly carfilzomib plus dexamethasone achieved a statistically significant higher overall response rate (62.9%) than patients who received the twice-weekly dose (40.8%),” Dr Mateos said.
Similarly, more patients achieved a complete response or better (7.1%) with the once-weekly dose than the twice-weekly dose (1.7%).
Safety
The overall safety profile was comparable between the 2 treatment groups and no new safety risks were identified.
Grade 3 or higher adverse events occurred in 67.6% (once-weekly) and 61.7% (twice-weekly) of patients.
Treatment-related grade 5 adverse events occurred in 5 patients (2.1%) in the once-weekly group and in 2 patients (0.9%) in the twice-weekly group.
The incidence of grade 3 or higher hypertension and cardiac failure was similar in both groups.
“Exposure-adjusted incidence of grade 3 or higher adverse events was slightly higher in the once-weekly vs the twice-weekly group,” Dr Mateos explained, “but the exposure-adjusted incidence for severe adverse events and adverse events leading to discontinuation of carfilzomib or death were similar between the treatment groups,” she said.
The ARROW study was supported by Amgen Inc.