TY - JOUR
TI - Once-weekly (70 mg/m2) vs twice-weekly (56 mg/m2) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials
AU - Moreau, P.
AU - Stewart, K.A.
AU - Dimopoulos, M.
AU - Siegel, D.
AU - Facon, T.
AU - Berenson, J.
AU - Raje, N.
AU - Berdeja, J.G.
AU - Orlowski, R.Z.
AU - Yang, H.
AU - Ma, H.
AU - Klippel, Z.
AU - Zahlten-Kumeli, A.
AU - Mezzi, K.
AU - Iskander, K.
AU - Mateos, M.-V.
JO - Cancer Medicine
PY - 2020
VL - 9
TODO - 9
SP - 2989-2996
PB - Wiley-Blackwell Publishing Ltd
SN - 2045-7634
TODO - 10.1002/cam4.2945
TODO - carfilzomib;  carfilzomib;  oligopeptide, acute kidney failure;  aged;  Article;  cohort analysis;  comparative effectiveness;  controlled study;  dosage schedule comparison;  drug efficacy;  drug response;  drug safety;  female;  heart failure;  human;  hypertension;  major clinical study;  male;  median survival time;  multiple myeloma;  priority journal;  progression free survival;  relapse;  vein embolism;  comparative study;  dose response;  drug administration;  drug effect;  drug resistance;  follow up;  middle aged;  multicenter study (topic);  multiple myeloma;  pathology;  phase 3 clinical trial (topic);  prognosis;  randomized controlled trial (topic);  salvage therapy;  survival rate;  tumor recurrence, Aged;  Clinical Trials, Phase III as Topic;  Dose-Response Relationship, Drug;  Drug Administration Schedule;  Drug Resistance, Neoplasm;  Female;  Follow-Up Studies;  Humans;  Male;  Middle Aged;  Multicenter Studies as Topic;  Multiple Myeloma;  Neoplasm Recurrence, Local;  Oligopeptides;  Prognosis;  Randomized Controlled Trials as Topic;  Salvage Therapy;  Survival Rate
TODO - Combination of carfilzomib with dexamethasone (Kd) is approved for use in relapsed and/or refractory multiple myeloma (RRMM), with carfilzomib administered twice weekly at 56 mg/m2 (Kd56 BIW) or once weekly at 70 mg/m2 (Kd70 QW). Post hoc cross-trial comparisons were performed to compare efficacy and safety profiles of Kd70 QW vs Kd56 BIW dosing schedules using data from three trials of patients with RRMM: A.R.R.O.W., CHAMPION-1, and ENDEAVOR. To select for comparable patient populations, side-by-side efficacy and safety comparisons were performed in subgroups of patients with 2-3 prior lines of therapy who were not refractory to bortezomib. The overall response rate (ORR) was 69.9% (95% confidence interval [CI], 61.7-77.2) for Kd70 QW and 72.4% (95% CI, 65.9-78.2) for Kd56 BIW. Median progression-free survival (PFS) was 12.1 months (95% CI, 8.4-14.3) for Kd70 QW and 14.5 months (95% CI, 10.2—not evaluable) for Kd56 BIW. Frequency of grade ≥ 3 adverse events (AEs) was 67.6% for Kd70 QW and 85.3% for Kd56 BIW. Regression analyses (adjusting for prognostic factors) of all patients in the trials who received Kd70 QW vs Kd56 BIW estimated a PFS hazard ratio of 0.91 (95% CI, 0.69-1.19; P =.47) and an ORR odds ratio of 1.12 (95% CI, 0.74-1.69; P =.61). These results suggest that Kd70 QW has a comparable efficacy profile compared with Kd56 BIW and represents a convenient and well-tolerated treatment for patients with RRMM. © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
ER -