Phase III ENDEAVOR trial results of Kyprolis (carfilzomib) in multiple myeloma published in The Lancet Oncology- Amgen

Amgen announced that results from an overall survival (OS) analysis of the Phase III head-to-head ENDEAVOR trial in multiple myeloma were published online first in The Lancet Oncology. Data showed that Kyprolis (carfilzomib) administered at 56 mg/m2 twice weekly and dexamethasone (Kd56) reduced the risk of death by 21 percent over Velcade (bortezomib) and dexamethasone (Vd), resulting in a 7.6 month OS benefit (median OS 47.6 months for Kd56 versus 40.0 for Vd, HR=0.79; p=0.01). The OS benefit was consistent regardless of prior Velcade therapy (HR=0.75 for no prior Velcade; HR=0.84 for prior Velcade).

This Kd56 regimen is already approved in the U.S., European Union and other countries based on the primary analysis of progression-free survival (PFS) in the ENDEAVOR study. Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. Notably, rates of grade 2 or higher peripheral neuropathy, a frequent dose-limiting toxicity of Velcade, were five-times lower in patients receiving Kd56 versus patients receiving Vd (7 percent versus 35 percent, respectively).

The most common adverse events (greater than or equal to 20 percent) in the Kyprolis arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache. As previously published in The Lancet Oncology, patients treated with Kd56 also achieved PFS of 18.7 months compared to 9.4 months in those receiving Vd, meeting the primary endpoint of the study (HR=0.53; 95 percent CI: 0.44 – 0.65; p<0.0001).

See: Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial.