Τίτλος:
Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods: Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results: Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion: KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse. © 2018 by American Society of Clinical Oncology.
Συγγραφείς:
Siegel, D.S.
Dimopoulos, M.A.
Ludwig, H.
Facon, T.
Goldschmidt, H.
Jakubowiak, A.
San-Miguel, J.
Obreja, M.
Blaedel, J.
Stewart, A.K.
Περιοδικό:
Journal of Clinical Oncology
Εκδότης:
American Society of Clinical Oncology
Λέξεις-κλειδιά:
bendamustine; bortezomib; carfilzomib; cisplatin; cyclophosphamide; dexamethasone; doxorubicin; lenalidomide; melphalan; pomalidomide; prednisone; thalidomide; antineoplastic agent; carfilzomib; dexamethasone; lenalidomide; oligopeptide, acute kidney failure; adult; anemia; Article; backache; bronchitis; cancer growth; cancer mortality; cancer recurrence; comparative study; constipation; controlled study; coughing; diarrhea; drug dose regimen; drug efficacy; drug withdrawal; fatigue; female; fever; heart failure; human; hypertension; hypokalemia; insomnia; ischemic heart disease; major clinical study; male; multicenter study; multiple cycle treatment; multiple myeloma; muscle spasm; nausea; neutropenia; outcome assessment; overall survival; peripheral neuropathy; phase 3 clinical trial; pneumonia; priority journal; progression free survival; randomized controlled trial; survival time; thrombocytopenia; treatment outcome; upper respiratory tract infection; viral upper respiratory tract infection; mortality; multiple myeloma; pathology; survival analysis; tumor recurrence, Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Female; Humans; Lenalidomide; Male; Multiple Myeloma; Neoplasm Recurrence, Local; Oligopeptides; Survival Analysis
DOI:
10.1200/JCO.2017.76.5032
