Interim results from ASPIRE, a randomized, open-label, multicenter phase 3 study
PUBLISHED: 2015-11-30  422 total views, 2 today

Keith Stewart1, S. vincent Rajkumar2, Meletios a.Dimopoulos3Tamás Masszi4, Ivan Špička5, Albert Oriol6, Roman Hájek7, Laura Rosiñol8, David Siegel9, Georgi g. Mihaylov10,

Vesselina Goranova-marinova11, Péter Rajnics12, Aleksandr Suvorov13, Ruben Niesvizky14, Andrzej j. Jakubowiak15, Jesus f. San miguel16, Heinz Ludwig17, Naseem Zojwalla18, Margaret e. Tonda18BiaoXing18, Philippe Moreau19, Antonio Palumbo20

1Division of Hematology–Oncology, Mayo Clinic, 2Mayo Clinic, 3Alexandra Hospital, 4St István and St Laszlo Hospital, 5General University Hospital in Prague, 6Hospital Germans Trias iPujol, Institut Català d’Oncologia, 7University of Ostrava,University Hospital Brno and Faculty of Medicine, 8Hospital Clínic deBarcelona, 9John Theurer CancerCenter at Hackensack University, 10Queen Joanna University Hospital, 11Hematology Clinic University Multiprofile Hospital for Active Treatment, 12Mór Kaposi Teaching Hospital, 13First Republican Clinical Hospital of Udmurtia, 14Weill Cornell Medical College, 15University of ChicagoMedical Center, 16Clinica Universidad de Navarra, 17Wilhelminenspital, Wilhelminen Cancer Research Institute, 18Inc., Onyx Pharmaceuticals,19University of Nantes, 20University of Torino.

 


Objective:Rd is a reference treatment for patientswith RMM. KRd has shown efficacy in a phase 1/2 study in RMM (Wang et al. Blood2013; 122:3122-3128). The ASPIRE study is comparing KRd with Rd in patientswith RMM. Method: Adults with RMM (1-3 prior regimens; N=792) wererandomized (1:1) to KRd or Rd. All patients received lenalidomide (25mg) ondays (D) 1-21 and dexamethasone (40 mg) on D1, 8, 15, 22 (28-day cycle [C]).KRd patients also received carfilzomib on D1, 2, 8, 9, 15, 16 during C1-12 (20mg/m2 [D1, 2 of C1]; 27 mg/m2 thereafter); carfilzomibwas omitted on D8, 9 during C13-18 and was not administered beyond C18. Theprimary endpoint is progression-free survival (PFS). Secondary endpointsinclude overall survival (OS), overall response rate (ORR; ≥partial response),duration of response (DOR), health-related quality of life (HR-QoL), andsafety. Result: Median treatment exposure was 22 cycles (KRd) and 14cycles (Rd). PFS was significantly improved with carfilzomib (hazard ratio[HR]=0.69; 95% confidence interval [CI]: 0.57–0.83; P<.0001), with a longer duration of median PFS for KRd vs. Rd(26.3 vs 17.6 months, respectively). Median OS was not reached (HR=0.79, 95%CI,0.63-0.99); Kaplan-Meier 24-month OS event-free rates were 73.3% (KRd) and65.0% (Rd) at an interim analysis. ORRs were 87.1% (KRd) and 66.7% (Rd) (P<.0001); 31.8% (KRd) vs 9.3% (Rd)achieved a ≥complete response; 14.1% and 4.3% achieved a stringent completeresponse. Median DOR was 28.6 (KRd) and 21.2 months (Rd). KRd improved HR-QoLcompared with Rd over 18 cycles of treatment (P=.0001). Grade ≥3 adverse events (AEs) were reported in 83.7% and80.7% of KRd and Rd patients, respectively; 15.3% and 17.7% of patients,respectively, discontinued treatment owing to AEs. Conclusion: Inpatients with RMM, KRd resulted in a clinically meaningful and statisticallysignificant improvement in PFS compared with Rd and had a favorablebenefit-risk profile. Patients continue to be followed for survival.

 


KeyWords: Carfilzomib, Lenalidomide, Multiplemyeloma


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