A regimen of carfilzomib (Kyprolis, Amgen), lenalidomide, and dexamethasone reduced the risk of death by 21% for relapsed multiple myeloma patients compared with treatment by lenalidomide and dexamethasone alone, according to final analysis of the phase 3 ASPIRE trial.
Amgen said the study met the key secondary endpoint of overall survival (OS) by demonstrating that carfilzomib, lenalidomide, and dexamethasone (KRd) led to a median OS of 48.3 months compared with 40.4 months for lenalidomide and dexamethasone alone (Rd) (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67–0.95). Per protocol, patients received 18 cycles of KRd before continuing treatment with Rd alone to progression. This KRd regimen of twice-weekly carfilzomib administered at 27 mg/m2 is approved in the U.S., European Union, and other countries based on the primary analysis of progression-free survival (PFS) in the ASPIRE study.
Kyprolis-based regimens are the first and only to demonstrate improved OS versus today's standards of care in two phase 3 studies in relapsed multiple myeloma, Amgen said.
"For multiple myeloma patients, the first relapse is usually the most devastating," said David S. Siegel, MD, PhD, chief of the Division of Multiple Myeloma at John Theurer Cancer Center in Hackensack, New Jersey, and investigator on the ASPIRE trial. "These data clearly show that the addition of Kyprolis—for just 18 cycles—to lenalidomide and dexamethasone at relapse gave patients a significantly improved chance of survival."
Adverse events observed in this updated analysis were consistent with those previously reported for ASPIRE. The most common adverse events (greater than or equal to 20%) in the Kyprolis arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia, and bronchitis.
Amgen recently announced OS results from the phase 3 head-to-head ENDEAVOR trial, which showed Kyprolis at 56 mg/m2 in combination with dexamethasone reduced the risk of death by 21% over bortezomib (Velcade, Millennium Pharmaceuticals) and dexamethasone (Vd). Patients treated with Kyprolis lived 7.6 months longer than those treated with Velcade (median OS, 47.6 months for Kd versus 40.0 months for Vd; HR, 0.79; 95% CI, 0.65–0.96).
The ASPIRE OS data will be submitted to a future medical conference, for publication, and to regulatory agencies worldwide to support a potential label update.
Source: Amgen; July 12, 2017.