Kyprolis (carfilzomib) in combination with low-dose dexamethasone is superior to Velcade (bortezomib) plus low-dose dexamethasone for the treatment of patients with relapsed multiple myeloma, a planned interim analysis from the phase III head-to-head ENDEAVOR trial has shown.1
Multiple myeloma is a cancer formed by malignant plasma cells in the bone marrow.
The American Cancer Society estimates that there will be about 26,850 new cases of multiple myeloma diagnosed in the United States in 2015 and about 11,240 deaths as a result of the disease.2
Kyprolis and Velcade are both proteasome inhibitors with Kyprolis being initially approved in 2012 by the U.S. Food and Drug Administration (FDA) for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent, such as lenalidomide, whose disease has progressed on or within 60 days of completion of last therapy.3
Velcade was initially approved by the FDA in 2003 for the treatment of patients with multiple myeloma.4
For the multicenter, open-label, phase III study, researchers enrolled 929 patients with relapsed multiple myeloma and randomly assigned them to receive Kyprolis 20 mg/m2 on days 1 and 2, followed by 56 mg/m2 on days 8, 9, 15, and 16 for the 28-day cycle 1 only plus dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 or Velcade 1.3 mg/m2 SC or IV on days 1, 4, 8, and 11 plus dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.
Patients who tolerated Kyprolis at 56 mg/m2 in cycle 1 were kept at that dose for further cycles.1
Preliminary results show that patients with relapsed multiple myeloma who were treated with Kyprolis had a median progression-free survival of 18.7 months compared with 9.4 months in those treated with Velcade (HR=0.53; 95% CI: 0.44,0.65).
The findings demonstrate that patients with relapsed multiple myeloma treated with Kyprolis lived twice as long as those treated with Velcade without their cancer worsening.1
In regard to safety, treatment discontinuation due to adverse events and on-study deaths were similar between the Kyprolis and Velcade arms. Cardiac and renal failure occurred more commonly in the Kyprolis arm than the Velcade arm.
Hypertension and dyspnea were also more common in patients treated with Kyprolis.1 The most common adverse events associated with Kyprolis use are fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia.3
“As new treatment options become available to patients with relapsed multiple myeloma, comparative trials, like ENDEAVOR, are becoming increasingly important to help physicians make informed decisions about the optimal care for patients,” said Pablo J. Cagnoni, MD, President of Onyx Pharmaceuticals, Inc.
“Demonstrating superiority over Velcade in this head-to-head trial supports our goal of ensuring continued improvement of patient outcomes and potentially establishing Kyprolis as the backbone of therapy for patients with multiple myeloma.”1
Overall survival data are not yet mature and full data will be submitted for presentation at the 2015 American Society of Clinical Oncology Annual Meeting in Chicago, IL, in May.1
- Phase 3 head-to-head ENDEAVOR study demonstrates superiority of Kyrolis (cafilzomib) over Velcade (bortezomib) in patients with relapsed multiple myeloma. Amgen. https://www.amgen.com/media/media_pr_detail.jsp?year=2015&releaseID=2021291. Published March 1, 2015. Accessed March 5, 2015.
- What are the key statistics about multiple myeloma? American Cancer Society. http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Published Jan 23, 2015. Accessed March 5, 2015.
- Kyprolis (carfilzomib) [package insert]. South San Francisco, CA: Onyx Pharmaceuticals, Inc. http://www.kyprolis.com/prescribing-information.
- Velcade (bortezomib) [package insert]. Cambridge, MA: Millennium Pharmaceuticals, Inc. http://www.velcade.com/Files/PDFs/VELCADE_PRESCRIBING_INFORMATION.pdf.