Superior Efficacy of Carfilzomib and Dexamethasone (Kd56) Vs Bortezomib and Dexamethasone (Vd) in Multiple Myeloma (MM) Patients with Moderate or Serious Renal Failure: A Subgroup Analysis of the Phase 3 Endeavor Study

Abstract

Abstract Background: Carfilzomib, a second generation selective proteasome inhibitor, is approved in the United States and other countries for the treatment of relapsed or refractory multiple myeloma (RRMM). In the randomized, phase 3 study ENDEAVOR, Kd56 demonstrated clinically and statistically significant improvement compared with Vd in both progression-free survival (PFS) (median 18.7 vs 9.4 months [mos]; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.44-0.65; 1-sided P Methods: Adults with RRMM (1-3 prior regimens) and creatinine clearance (CrCL) ≥15 mL/min were eligible for the ENDEAVOR trial. The Cockcroft-Gault formula was used to calculate baseline, and on study, renal function. In the Kd56 arm, pts received carfilzomib (30-min intravenous [IV] infusion) on days (D) 1, 2, 8, 9, 15, and 16 (20 mg/m2 on D1, 2 [cycle 1]; 56 mg/m2 thereafter) and dexamethasone (20 mg) on D1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles. Pts in the Vd arm received bortezomib (1.3 mg/m2; IV or subcutaneously) on D1, 4, 8, and 11 and dexamethasone (20 mg) on D1, 2, 4, 5, 8, 9, 11, and 12 of 21-day cycles. Pts were treated until disease progression, physician decision, unacceptable toxicity, withdrawal of consent, or mortality. The primary end point was PFS; secondary end points included OS, overall response rate (ORR), duration of response, rate of grade ≥2 peripheral neuropathy (PN), and safety. The present analyses examined efficacy and safety outcomes in pts grouped according to baseline renal function (CrCL ≥15 to Results: A total of 929 pts were enrolled (CrCL ≥15 to Conclusions: To our knowledge, ENDEAVOR is the largest randomized trial in RRMM to have included pts with severe renal impairment. Superior efficacy for Kd56 vs Vd was observed across all renal subgroups. The safety profile was consistent with the findings from the previous interim analysis. Overall, these data suggest that Kd56 has a favorable benefit-risk profile and should be considered as the new standard of care in pts with RRMM, regardless of baseline renal function. Download : Download high-res image (203KB) Download : Download full-size image Disclosures Dimopoulos: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology: Consultancy, Honoraria, Other: Advisory Committee: Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Onyx Pharmaceuticals, an Amgen subsidiary, Takeda Oncology; Genesis Pharma: Research Funding; Novartis: Consultancy, Honoraria. Siegel: Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau; Merck: Consultancy. White: Bristol-Myers Squibb: Consultancy, Honoraria; Amgen, Celgene, Janssen, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Boccia: Pfizer Inc., Sandoz: Other: Advisory Board. Yang: Amgen Inc.: Employment, Equity Ownership. Kimball: Amgen: Employment, Equity Ownership. Iskander: Amgen: Employment, Equity Ownership. Mezzi: Amgen, Inc.: Employment, Equity Ownership. Ludwig: Janssen-Cilag: Consultancy, Speakers Bureau; Bristol-Meyers: Speakers Bureau; AMGEN: Consultancy, Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau. Niesvizky: Amgen: Consultancy; Celgene: Consultancy; BMS: Consultancy; Janssen: Consultancy.