Positive results from a planned overall survival ( OS ) interim analysis of the phase 3 head-to-head ENDEAVOR trial were presented. The study met the key secondary endpoint of overall survival, demonstrating that patients with relapsed or refractory multiple myeloma treated with Carfilzomib ( Kyprolis ) and Dexamethasone [ CD regimen ] lived 7.6 months longer than those treated with Bortezomib ( Velcade ) and Dexamethasone [ BD regimen ] ( median OS 47.6 months for Carfilzomib and Dexamethasone versus 40.0 for Bortezomib and Dexamethasone, hazard ratio, HR = 0.79, 95% CI, 0.65 – 0.96 ).
The CD regimen administered with 56 mg/m2 Carfilzomib twice weekly 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.
These results confirm the superiority of Carfilzomib over Bortezomib in relapsed or refractory multiple myeloma patients.
ENDEAVOR is the only study to demonstrate a survival benefit in a head-to-head comparison with a current standard of care regimen.
Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. 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.
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 Carfilzomib in combination with low-dose Dexamethasone, versus Bortezomib with low-dose Dexamethasone 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 progression-free survival ( 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.
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse. It is a rare and very aggressive disease that accounts for approximately 1% of all cancers.
In the U.S., there are nearly 95,000 people living with, or in remission from, multiple myeloma. Approximately 30,330 Americans are diagnosed with multiple myeloma each year and 12,650 patient deaths are reported on an annual basis.
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.
Carfilzomib has been shown to block proteasomes, leading to an excessive build-up of proteins within cells. In some cells, Carfilzomib can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins. ( Xagena2017 )
Source: Amgen, 2017