FDA Approves Carfilzomib as Single Agent or in Combination in Relapsed/Refractory Multiple Myeloma
Amgen announced on January 21 that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application of carfilzomib (Kyprolis) for injection in combination with dexamethasone or with lenalidomide (Revlimid) plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. The FDA also approved carfilzomib as a single agent for the treatment of patients with relapsed or refractory multiple myeloma that have received one or more lines of therapy. This FDA decision converts to full approval the initial accelerated approval carfilzomib received in July 2012 as a single agent.
Study Results
The approval is based on results from the phase III head-to-head ENDEAVOR study. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. The data showed patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone achieved 50% greater progression-free survival of 18.7 months compared to 9.4 months in those receiving bortezomib (Velcade) and dexamethasone (hazard ratio [HR] = 0.53, 95% [confidence interval] CI = 044–0.65, P < .0001), a current standard of care. Improvement in progression-free survival in carfilzomib and dexamethasone arm was seen across all pre-specified subgroups, including bortezomib-naive patients, those with high- or standard-risk cytogenetics, and with or without prior transplantation.
Carfilzomib and dexamethasone also demonstrated improvement over bortezomib and dexamethasone for secondary endpoints, achieving a higher overall response rate (77% vs 63%, P < .0001) and lower rate of grade 2 or higher neuropathy events (6% [95% CI = 4–8] vs 32% [95% CI = 28–36]). In the carfilzomib and bortezomib groups, 54.3% and 28.6% of patients achieved a very good partial response or better (P < .0001), and 12.5% and 6.2% of patients achieved a complete response or better (P < .0001), respectively. Overall survival data are not yet mature and continue to be monitored.
Adverse Events
Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. A number of known adverse drug reactions were reported at a higher rate in the carfilzomib group compared with the bortezomib group, including any-grade dyspnea, hypertension, pyrexia, and cough, as were any-grade cardiac failure (grouped term; 8% vs 3%) and acute renal failure (grouped term; 8% vs 5%).
Rates of grade 3 or higher adverse events were 73% in the carfilzomib group and 67% in the bortezomib group. Grade 3 or higher adverse events of interest in the carfilzomib and bortezomib groups included hypertension (9% vs 3%), dyspnea (5% vs 2%), cardiac failure (5% vs 2%), acute renal failure (4% vs 3%), ischemic heart disease (2% vs 2%) and pulmonary hypertension (0.6% vs 0.2%).
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
