The first interim analysis had reported that progression-free survival was significantly longer with carfilzomib administered in combination with dexamethasone than with bortezomib and dexamethasone. The researchers say that to their knowledge, carfilzomib is the first and only multiple myeloma treatment that extends overall survival in the relapsed setting over the current standard of care.
A commentary notes that a disadvantage of carfilzomib is the need for intravenous administration twice a week, however a more convenient administration schedule of once a week has been assessed in the CHAMPION-1 study with encouraging safety and efficacy results. On the basis of these data, the ARROW study was initiated, which will assess carfilzomib combined with dexamethasone given once versus twice a week in relapsed and refractory multiple myeloma. It suggests that overall, the ENDEAVOR study indicates that carfilzomib and dexamethasone is an effective two-drug combination that should be considered in patients with multiple myeloma who have received more than one previous line of therapy. It adds however that several other combinations have recently been approved in the relapsed or refractory setting (triple regimens of lenalidomide–dexamethasone combined with either carfilzomib, ixazomib, daratumumab, or elotuzumab, as well as panobinostat or daratumumab combined with bortezomib–dexamethasone). It suggests that in the absence of head-to-head comparisons, choice of therapy depends on patient characteristics (age, comorbidities, and performance status), tumour-related features (cytogenetics, and aggressiveness of relapse), and type of and response to previous treatments. It calls for development of biomarkers that predict response, survival, and toxicity of these different regimens to guide treatment choices in individual patients. Another important question that needs addressing is the optimal sequence of available therapies.