Carfilzomib + Melphalan, Prednisone Fails to Improve PFS in Myeloma
Adding carfilzomib to melphalan and prednisone is not superior to bortezomib, melphalan, prednisone for improving progression-free survival.
Adding carfilzomib to melphalan and prednisone (KMP) is not superior to bortezomib, melphalan, prednisone (VMP) for improving progression-free survival among newly-diagnosed patients with multiple myeloma ineligible to undergo hematopoietic stem cell transplantation (HSCT).1
The multicenter, open-label, phase 3 CLARION trial (Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma; ClinicalTrials.gov Identifier: NCT01818752) randomly assigned 955 HSCT-ineligible patients with newly diagnosed multiple myeloma to receive KMP or VMP for 54 weeks.
Preliminary results showed that median progression-free survival was 22.3 months with KMP compared with 22.1 months with VMP. Though not yet mature, there was also no statistically significant difference in overall survival between the 2 treatment arms.
The adverse events observed in the KMP arm were consistent with previous reports of carfilzomib's safety profile. Nearly 75% of patients in the KMP arm experienced grade 3 or worse adverse events, versus about 76% in the VMP arm. Substantially more patients (35.1%) of patients in the VMP arm reported grade 2 or worse peripheral neuropathy than those who received KMP (2.5%).
"Based on studies in the Kyprolis label, including the ENDEAVOR study, a head-to-head comparison of Kyprolis to Velcade in patients with relapsed or refractory multiple myeloma, we know Kyprolis to be a major advance in proteasome inhibitor therapy," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, stated in a press release. "The CLARION results, generated in the context of a melphalan-containing regimen, are disappointing, especially given the robust data we've seen in the second-line setting."
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Investigators are comparing the efficacy and safety of carfilzomib with that of bortezomib, in combination with lenalidomide and dexamethasone, among newly diagnosed patients with multiple myeloma as part of the phase 3 ENDURANCE trial (Bortezomib or Carfilzomib With Lenalidomide and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma; ClinicalTrials.gov Identifier: NCT01863550). The study is recruiting patients nationwide.
- Amgen announces top-line results from phase 3 Kyprolis (carfilzomib) CLARION study in newly diagnosed multiple myeloma patients. Amgen website. http://www.amgen.com/media/news-releases/2016/09/amgen-announces-topline-results-from-phase-3-kyprolis-carfilzomib-clarion-study-in-newly-diagnosed-multiple-myeloma-patients. Updated September 27, 2016. Accessed September 27, 2016.