medwireNews: Once-weekly treatment with carfilzomib at the maximum tolerated dose significantly delays disease progression compared with twice-weekly treatment at a lower dose in patients with relapsed or refractory multiple myeloma, study data show.
The once-weekly schedule did not raise any new safety concerns and is expected to “provide a more convenient dosing regimen for patients and lead to better adherence to treatment,” report Philippe Moreau (University Hospital Hotel-Dieu, Nantes, France) and colleagues in The Lancet Oncology.
They found that patients randomly assigned to receive the irreversible proteasome inhibitor carfilzomib at a dose of 70 mg/m2 once weekly (n=240) for 3 weeks of each 4-week cycle had a significant 31% lower risk for disease progression or death during follow-up than those assigned to receive 27 mg/m2 twice weekly (n=238), given on 2 consecutive days, for the same duration.
Indeed, median progression-free survival was 11.2 months with once-weekly dosing compared with 7.6 months with the twice-weekly schedule.
The patients additionally received dexamethasone 40 mg once weekly during the phase III A.R.R.O.W. trial and had previously been treated with at least one proteasome inhibitor and immunomodulatory agent.
The overall response rate was also significantly higher in the once-weekly group than in the twice-weekly group, at 62.9% versus 40.8%, as was the proportion of patients achieving a very good partial response or better, at 34.2% versus 13.4%.
Moreau and team note that this was a preplanned interim analysis, and that overall survival data were not yet mature. At 12 months, overall survival was 76.6% for the once-weekly group and 71.9% for the twice-weekly group, but “[p]atients will continue to be followed for mortality until the study is complete,” they remark.
There were more grade 3 or worse adverse events reported in the once-weekly group than in the twice-weekly group (68 vs 62%), but the investigators say that they were “consistent with the known safety profile of carfilzomib.”
Treatment related adverse events leading to discontinuation of carfilzomib occurred in 8% of patients in the once-weekly group and 5% of patients in the twice-weekly group, while treatment-related deaths occurred in 2% and 1%, respectively.
In an accompanying comment Holger Auner (Imperial College London, UK) and Kwee Yong (University College London, UK) say the study “will lead to the welcome availability of a more convenient once weekly dosing schedule, and represents an important milestone for future research employing once weekly carfilzomib in multiagent protocols, which are becoming the standard of care for treating multiple myeloma.”
According to the researchers “carfilzomib at 27 mg/m2 with dexamethasone was the most common carfilzomibbased treatment regimen used from 2012–14;” however, Auner and Yong point out that the current standard dose, based on the ENDEAVOR trial results, is 56 mg/m2.
Therefore, “it remains to be established how this compares with a dose of 70 mg/m2 once a week,” they add.
Moreau et al say they “plan to address the gap in the A.R.R.O.W. study in a future analysis by comparing once weekly carfilzomib at 70 mg/m2 plus dexamethasone with the approved standard of twice weekly carfilzomib at 56 mg/m2 plus dexamethasone.”
The study findings were also presented at the ASCO Annual Meeting 2018 in Chicago, Illinois, USA.
By Laura Cowen
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