Carfilzomib may significantly improve overall survival (OS) compared with bortezomib in patients with relapsed/refractory (R/R) multiple myeloma, according to a study published in the Lancet Oncology.
In the phase 3 ENDEAVOR trial (ClinicalTrials.gov Identifier: NCT01568866), the study authors randomly assigned 929 patients with R/R multiple myeloma to receive dexamethasone with carfilzomib 20 mg/m2 on cycle 1 and increased to 56 mg/m2 thereafter, or bortezomib 1.3 mg/m2.
The first interim analysis of ENDEAVOR demonstrated the superiority of carfilzomib over bortezomib in multiple outcomes, such as progression-free survival, objective response, and median duration of response. At the time of the first interim analysis however, OS data was not available as the median follow-up was set to approximately 12 months.
The second interim analysis revealed that median OS was 47.6 months (95% CI, 42.5-not evaluable) in the carfilzomib arm vs 40.0 months (95% CI, 32.6-42.3) in the bortezomib arm (hazard ratio [HR], 0.791; 95% CI, 0.6248-0.964; one-sided P =.010).
Grade 3 or worse adverse events (AE), such as anemia, hypertension, dyspnea, and decreased lymphocyte count were more frequently reported by the carfilzomib group than the bortezomib group. There were similar rates of pneumonia, thrombocytopenia, and fatigue. The frequency of grade 2 or worse peripheral neuropathy was significantly lower in the carfilzomib group.
The study authors concluded that “on the basis of these results, carfilzomib combined with dexamethasone should be considered a standard of care for patients with relapsed or refractory multiple myeloma.”
1. Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial [published online August 23, 2017]. Lancet Oncol. doi: 10.1016/S1470-2045(17)30578-8