Carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in pati
PUBLISHED: 2015-11-30  500 total views, 1 today

Meletios Dimopoulos1, Philippe Moreau2, AntonioPalumbo3Douglas Joshua4, Ludek Pour5, Roman Hájek5, Thierry Facon6, Heinz Ludwig7Albert Oriol8, Laura Rosiñol9, Jan Straub10, Aleksandr Suvorov11, Elena Rimashevskaya12, Katja Weisel13, Vesselina Goranova-Marinova14Anthony Schwarer15, Leonard Minuk16,Tamás Massz17, Ievgenii Karamanesht18, Massimo Offidani19, Vania Hungria20, Andrew Spencer21Heidi Gillenwater22, Shibao Feng22, Wee-joo Chng23

1Department of ClinicalTherapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece, 2University of Nantes, France, 3Universityof Torino, Italy, 4Royal Prince Alfred Hospital, 5UniversityHospital Brno, Czech, 6Chru Lille Hôpital Claude Huriez, 7WilhelminenCancer Research Institute, 8Institut Català d’oncologia, 9HospitalClínic de Barcelona, 10Vseobecna Fakultni Nemocnice v Praze, 11FirstRepublican Clinical Hospital, 12Semashko Central Clinical Hospital, 13UniversitatsklinikumTubingen, 14University Multiprofil, 15Box hill hospital, 16Londonhealth sciences centre, 17St. istvan and st. Laszlo Hospital, 18kyivCenter For Bone Marrow, 19Clinica di Ematologia, 20Irmandadeda Santa Casa de Misericór, 21Alfred Health-Monash University, 22OnyxHarmaceuticals,  23NationalUniversity Cancer Institute.

 


Objective:ENDEAVOR (NCT01568866) is comparing Kdwith Vd in patients with RMM. The primary endpoint is PFS. Secondary endpointsinclude OS, ORR, peripheral neuropathy (PN) rate, and safety. Method: Adultswith RMM (1-3 prior treatments) were eligible. Patients were randomized 1:1 andstratified by prior proteasome inhibitor treatment, prior lines of treatment,ISS stage, and intended route of V administration (if randomized to Vd). The Kdarm received K (30‑min IV infusion) on days (D) 1, 2, 8, 9, 15, 16 of a 28-daycycle (20mg/m2 on D1, 2 [cycle 1]; 56mg/m2 thereafter)and dexamethasone (20 mg) on D1, 2, 8, 9, 15, 16, 22, 23. The Vd arm received V(1.3mg/m2; IV or SC on D1, 4, 8, 11 of a 21-day cycle) anddexamethasone (20mg) on D1, 2, 4, 5, 8, 9, 11, 12. Cycles were repeated untildisease progression or unacceptable toxicity. Result: Data are presentedfor Kd then Vd. In total, 929 patients (Kd: 464; Vd: 465) were randomized. Inthe Vd arm, 83.6% of patients received SC V. At the preplanned interimanalysis, Kd showed a significant improvement in median PFS vs Vd (18.7 vs 9.4months; hazard ratio=0.53; P<.0001).OS data were immature and continue to be followed. ORRs were 76.9% and 62.6% (P<.0001); 54.3% and 28.6% had ≥VGPR;12.5% and 6.2% of patients had ≥CR. Treatment discontinuation due to an AEoccurred in 14.0% and 15.7% of patients. On-study death due to an AE occurredin 3.9% and 3.4% of patients. AEs of interest (grade ≥3) included hypertension(preferred term; 8.9% vs 2.6%), dyspnea (high-level term; 5.6% vs 2.2%),cardiac failure (grouped term; 4.8% vs 1.8%), and acute renal failure (groupedterm; 4.1% vs 2.6%). Grade ≥2 PN rates (grouped term) were 6.0% vs 32.0% (P<.0001). Conclusion: Kddemonstrated significant superiority over Vd in RMM, with a two-foldimprovement in median PFS, and had a favorable benefit-risk profile. K is apotential best-in-class agent for RMM.

 


KeyWords: Carfilzomib, Bortezomib, Multiple myeloma


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