Meletios Dimopoulos¹, Philippe Moreau², AntonioPalumbo³, Douglas Joshua⁴, Ludek Pour⁵, Roman Hájek⁵, Thierry Facon⁶, Heinz Ludwig⁷, Albert Oriol⁸, Laura Rosiñol⁹, Jan Straub¹⁰, Aleksandr Suvorov¹¹, Elena Rimashevskaya¹², Katja Weisel¹³, Vesselina Goranova-Marinova¹⁴, Anthony Schwarer¹⁵, Leonard Minuk¹⁶,Tamás Massz¹⁷, Ievgenii Karamanesht¹⁸, Massimo Offidani¹⁹, Vania Hungria²⁰, Andrew Spencer²¹, Heidi 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