Proteasome Inhibitors Go Head-to-Head in Multiple Myeloma Study
A Phase 3 head-to-head trial (ENDEAVOR) of patients with relapsed or refractory multiple myeloma showed that a regimen of Kyprolis (carfilzomib; Amgen) and dexamethasone was associated with a longer overall survival (OS) rate when compared to bortezomib (Velcade; Millennium) and dexamethasone.
A total of 929 patients took part in the trial. The Kyprolis group received a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20mg). For Cycle 1 only, Kyprolis was administered at 20mg/m2 on days 1 and 2, and if tolerated was escalated to 56mg/m2 from day 8 Cycle 1 onwards. The other group received bortezomib (1.3mg/m2) with low-dose dexamethasone (20mg). Results showed a median OS of 47.6 months for the Kyprolis group versus 40.0 months for the bortezomib group (HR = 0.79, 95% CI, 0.65 – 0.96).
“These results confirm the superiority of Kyprolis over Velcade in relapsed or refractory multiple myeloma patients,” said Sean E. Harper, MD, EVP of Research and Development at Amgen. “A survival benefit has rarely been demonstrated in relapsed or refractory multiple myeloma. ENDEAVOR is the only study to demonstrate a survival benefit in a head-to-head comparison with a current standard of care regimen.”
Both carfilzomib and bortezomib are proteasome inhibitors. Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed. Blocking proteasomes leads to an excessive build-up of proteins within cells which can lead to cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.
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