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Carfilzomib regimen extends OS in relapsed multiple myeloma
The combination of carfilzomib and dexamethasone significantly extended OS compared with bortezomib and dexamethasone, according to results of a planned interim analysis of the phase 3 ENDEAVOR trial.
The trial — the only head-to-head comparison of proteasome inhibitors to demonstrate a statistically significant OS benefit — included 929 patients whose multiple myeloma relapsed after one to three prior therapeutic regimens.
Researchers randomly assigned patients to carfilzomib (Kyprolis, Amgen) plus dexamethasone or bortezomib (Velcade, Takeda Oncology) plus dexamethasone.
Patients in the carfilzomib group received IV carfilzomib (20 mg/m2 on days 1 and 2; 56 mg/m2 thereafter) plus 20 mg dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles. Patients in the bortezomib group received 1.3 mg/m2 IV or subcutaneous bortezomib on days 1, 4, 8, 11 and 21, plus 20 mg dexamethasone on days 1, 2, 4, 5, 8, 9, 11 and 12 in 21-day cycles.
PFS served as the primary endpoint. OS served as a secondary endpoint.
Previously published results showed the carfilzomib regimen significantly extended PFS (18.9 months vs. 9.4 months; P < .0001).
Results of the planned interim analysis — which will be presented March 4 at the International Myeloma Workshop in India — showed carfilzomib-treated patients also achieved longer median OS (47.6 months vs. 40 months; HR = 0.79; 95% CI, 0.65-0.96).
“These results confirm the superiority of carfilzomib over bortezomib in relapsed or refractory multiple myeloma patients,” Sean E. Harper, MD, executive vice president of research and development at Amgen, said in a company-issued press release. “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. These results further support carfilzomib as a foundational therapy in this patient population.”
The FDA previously approved the carfilzomib–dexamethasone regimen on the basis of the PFS results from ENDEAVOR.
Adverse events associated with carfilzomib appeared consistent with those reported in prior studies. The most common adverse events reported in prior trials of carfilzomib combination therapy were anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasms, cough, upper respiratory tract infection and hypokalemia.
“For an incurable disease like multiple myeloma, a major treatment goal for oncologists and hematologists is to help patients live as long as possible,” co-investigator Meletios A. Dimopoulos, MD, professor of clinical therapeutics at National and Kapodistrian University of Athens School of Medicine, said in the release. “Based on these data, we now know that carfilzomib not only significantly extended PFS compared with bortezomib, but also OS, making it a clinically meaningful advance in the treatment of relapsed or refractory multiple myeloma."