Carfilzomib Bests Bortezomib in Relapsed Multiple Myeloma

Results from the phase III, open-label, multicenter ENDEAVOR study support the use of the proteasome inhibitor, carfilzomib, in combination with dexamethasone in patients with relapsed multiple myeloma (MM) over bortezomib plus dexamethasone.

While the carfilzomib/dexamethasone combination (Kd) is approved in the United States for relapsed and refractory MM at 20/27 mg/m2 over 2-10 minutes, earlier-phase studies determined that a dose of 20/56 mg/m2 over 30 minutes (the maximum tolerated dose of Kd) led to higher response rates in this population, said study presenter Meletios A. Dimopoulos, MD, from the University of Athens in Greece during the 2015 American Society of Clinical Oncology Annual Meeting.

Patients were randomized 1:1 to cycles of Kd or bortezomib/dexamethasone (Vd) repeated until disease progression or unacceptable toxicity. All 929 patients in the study had received up to three prior treatments, and nearly one-fourth had high-risk cytogenetic features.

After a median follow-up of 11.2 months, the primary endpoint of progression-free survival (PFS) was 18.7 months for Kd and 9.4 months for Vd (p<0.0001), with twice as many patients achieving a complete response (CR; 13% vs. 6%) or very good partial response (VGPR; 54% vs. 29%).

While Kd had increased rates of grade ≥3 hypertension (9% vs. 3%), dyspnea (5% vs. 2.2%), and cardiac failure (5% vs. 1.8%) than Vd, rates of grade ≥2 peripheral neuropathy were significantly lower with Kd (6% vs. 32%; p<0.0001).

“Carfilzomib with dexamethasone was superior to bortezomib with dexamethasone regardless of age or prior bortezomib exposure,” Dr. Dimopoulos concluded, noting that the drug combination could represent a new standard of care for MM.


Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed multiple myeloma (RMM): Results from the phase III study ENDEAVOR. Abstract #8509. Presented at the 2015 American Society of Clinical Oncology Annual Meeting; June 1, 2015; Chicago, IL.