Europe’s Committee for Medicinal Products for Human Use (CHMP) recommended approval for carfilzomib in combination with dexamethasone for patients with multiple myeloma who have been treated with at least one prior therapy.
The recommendation was based on the results of the phase III ENDEAVOR study that included 929 patients who were randomized to receive:
- Carfilzomib 20 mg/m2 administered as a 30-minute infusion on days 1 and 2 of cycle 1 with a dose escalation to 56 mg/m2 on day 8 of cycle 1 (if the original dose was tolerated), followed by 56 mg/m2 on days 9, 15, and 16 throughout subsequent cycles plus dexamethasone (n=464)
- Bortezomib and dexamethasone (n=465)
Carfilzomib plus dexamethasone led to a 47 percent decreased risk of disease progression compared with bortezomib and dexamethasone. The median progression-free survival (PFS; primary endpoint) was 18.7 months for carfilzomib plus dexamethasone compared with 9.4 months for bortezomib plus dexamethasone (hazard ratio [HR] = 0.53; 95% CI 0.44-0.65; p<0.0001).
Grade 3 adverse events (AEs) and serious AEs occurred more frequently in the carfilzomib combination cohort (73% vs. 67% and 54% vs. 29%, respectively). However, dose reductions occurred more frequently in the bortezomib plus dexamethasone cohort (48% vs. 23%). Treatment discontinuation and deaths were comparable in the two groups.
Grade ≥3 hematologic AEs were similar between the two groups and included anemia, thrombocytopenia, neutropenia, upper respiratory infection, and pneumonia, while non-hematologic AEs included diarrhea, fatigue, dyspnea, pyrexia, constipation, and insomnia.
Source: Amgen press release, May 27, 2016.