Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials

• Published in: International journal of hematology Vol. 110; no. 4; pp. 466 - 473
• Main Authors: Dimopoulos, Meletios A., Moreau, Philippe, Iida, Shinsuke, Huang, Shang-Yi, Takezako, Naoki, Chng, Wee Joo, Zahlten-Kumeli, Anita, Sersch, Martina A., Li, Julia, Huang, Mei, Lee, Jae Hoon
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2019; Springer Nature B.V
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asian Continental Ancestry Group; Bortezomib; Bortezomib - administration & dosage; Clinical trials; ClinicalTrials.gov; Dexamethasone; Dexamethasone - administration & dosage; Drug Administration Schedule; Hematology; Humans; Inhibitor drugs; Medicine; Medicine & Public Health; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; NCT01568866; NCT02412878; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Oncology; Original Article; Proteasome inhibitors; Proteasome Inhibitors - administration & dosage; Proteasome Inhibitors - adverse effects; Randomization; Risk Assessment; Slopes; Subgroups; Survival; Survival Rate; Targeted cancer therapy; Treatment Outcome; Carfilzomib; Clinical trials; Relapsed and/or refractory multiple myeloma; Asian population
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-019-02704-z

Carfilzomib is an irreversible proteasome inhibitor used for the treatment of relapsed and/or refractory multiple myeloma (RRMM). We evaluated the efficacy and safety of carfilzomib in subgroups of Asian patients in the randomized phase 3 ENDEAVOR and A.R.R.O.W. trials. In ENDEAVOR, patients received carfilzomib twice-weekly (56 mg/m 2 ) plus dexamethasone (Kd; n  = 56) or bortezomib plus dexamethasone (Vd; n  = 57). In A.R.R.O.W., patients received carfilzomib once-weekly (70 mg/m 2 , n  = 30) or twice-weekly (27 mg/m 2 , n  = 15) plus dexamethasone. Median progression-free survival (PFS) among Asian patients in ENDEAVOR was longer with Kd than with Vd (14.9 versus 8.8 months; HR 0.599); the overall response rate (ORR) was 80.4% versus 70.2%. Median overall survival (Kd versus Vd) was 47.6 versus 38.8 months (HR 0.856). Median PFS among Asian patients in A.R.R.O.W. was longer for once-weekly versus twice-weekly Kd (16.0 versus 8.4 months; HR 0.628); ORR was 76.7% versus 53.3%. Rates of grade ≥ 3 adverse events were 89.1% (Kd) and 89.5% (Vd) in ENDEAVOR, and 76.6% (once-weekly Kd) versus 73.3% (twice-weekly Kd) in A.R.R.O.W. Overall, carfilzomib had a favorable benefit-risk profile across both dosing regimens [once-weekly (Kd 70 mg/m 2 ) and twice-weekly (Kd 56 mg/m 2 )] in Asian patients with RRMM, which was consistent with the results of both parent studies. Trial registration ClinicalTrials.gov: NCT01568866, NCT02412878.