Carfilzomib (Kyprolis, Amgen) reduced the risk of death by 21% compared with bortezomib (Velcade, Millennium Pharmaceuticals) in patients with relapsed or refractory multiple myeloma who received one of the two drugs in combination with dexamethasone in the phase 3 head-to-head ENDEAVOR trial, Amgen says.
Amgen announced that results from an overall survival (OS) analysis of the ENDEAVOR trial were published online first in The Lancet Oncology. Data showed that carfilzomib administered at 56 mg/m2 twice weekly and dexamethasone (Kd56) reduced the risk of death by 21% compared with bortezomib and dexamethasone (Vd). That resulted in a 7.6 month OS benefit (median OS, 47.6 months for Kd56 versus 40.0 for Vd, hazard ratio [HR], 0.79; P = 0.01). The OS benefit was consistent regardless of prior bortezomib therapy (HR, 0.75 for no prior bortezomib and 0.84 for prior bortezomib). This Kd56 regimen is already approved in the U.S. and other countries based on the primary analysis of progression-free survival (PFS) in the ENDEAVOR study.
"These results support the use of Kyprolis and dexamethasone as a standard of care for multiple myeloma patients at first relapse," said study coauthor and investigator Meletios A. Dimopoulos, MD, Professor of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine.
ENDEAVOR is the only head-to-head trial comparing proteasome inhibitors, Amgen noted.
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 carfilzomib, were five times lower in patients receiving Kd56 versus patients receiving Vd (7% versus 35%, respectively). The most common adverse events (greater than or equal to 20%) in the carfilzomib 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% confidence interval, 0.44–0.65; P
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kd56 versus Vd in patients whose multiple myeloma has relapsed after at least one, but not more than three, prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death.
Patients received treatment until progression with carfilzomib as a 30-minute infusion on days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, along with low-dose dexamethasone (20 mg). For Cycle 1 only, carfilzomib was administered at 20 mg/m2 on days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 Cycle 1 onwards. Patients who received bortezomib (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with bortezomib administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of bortezomib. More than 75% of the patients in the control arm received bortezomib subcutaneously. This study was conducted at 235 sites worldwide.
Source: Amgen; August 23, 2017.