Research in context
Evidence before this study
Bortezomib and dexamethasone is a standard treatment option worldwide for patients with multiple myeloma. We searched PubMed for clinical studies in multiple myeloma that have assessed carfilzomib with dexamethasone in patients with relapsed or refractory multiple myeloma. Specific search terms included “carfilzomib”, “dexamethasone”, “relapsed”, “refractory”, “second-line”, “third-line”, “salvage”, and “multiple myeloma”. We included all English language studies published until June 14, 2015.
We identified two studies that assessed the combination of carfilzomib and dexamethasone in patients with advanced multiple myeloma. In a phase 1b/2 study, carfilzomib showed promising activity and tolerability in combination with dexamethasone in patients with relapsed or refractory multiple myeloma or both. In a phase 2 study, treatment with carfilzomib with or without dexamethasone resulted in a high overall response and durable disease control in heavily pretreated patients with relapsed or refractory multiple myeloma, but was also associated with hypertension and heart failure. These studies suggested that carfilzomib with dexamethasone is a promising treatment option for patients with relapsed or refractory multiple myeloma.
Added value of this study
To our knowledge, ENDEAVOR is the first phase 3 head-to-head comparison between two proteasome inhibitors and is the largest phase 3 randomised trial to date in patients with relapsed or refractory multiple myeloma. In this study, patients treated with carfilzomib and dexamethasone had longer progression-free survival compared with those treated with bortezomib and dexamethasone. Overall, the results from ENDEAVOR suggest an important role for carfilzomib-based regimens for the treatment of patients with relapsed or refractory multiple myeloma.
Implications of all the available evidence
Compared with bortezomib and dexamethasone, carfilzomib with dexamethasone was associated with a significant and clinically meaningful improvement in progression-free survival. Furthermore, carfilzomib with dexamethasone had an acceptable adverse event profile. These results delineate the favourable benefit–risk profile of this regimen. Carfilzomib and dexamethasone should be considered as a treatment option for patients with multiple myeloma for whom bortezomib and dexamethasone could also be considered.