|Title||Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, Essell J, Gaffar Y, Warr T, Neuwirth R, Zhu Y, Elliott J, Esseltine D-L, Niculescu L, Reeves J|
|Journal||J Clin Oncol|
|Date Published||2015 Nov 20|
|Keywords||Adrenal Cortex Hormones, Aged, Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Community Health Services, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multiple Myeloma, Multivariate Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Severity of Illness Index, Survival Analysis, Thalidomide, Treatment Outcome|
PURPOSE: The US community-based, phase IIIB UPFRONT trial was designed to compare three frontline bortezomib-based regimens in transplantation-ineligible patients with myeloma.
PATIENTS AND METHODS: Patients (N = 502) were randomly assigned 1:1:1 to 24 weeks (eight 21-day cycles) of induction with bortezomib-dexamethasone (VD; n = 168; intravenous bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11 plus oral dexamethasone 20 mg, days 1, 2, 4, 5, 8, 9, 11, and 12 [cycles 1 to 4], or 1, 2, 4, and 5 [cycles 5 to 8]), bortezomib-thalidomide-dexamethasone (VTD; n = 167; bortezomib and dexamethasone as before plus oral thalidomide 100 mg, days 1 to 21), or bortezomib-melphalan-prednisone (VMP; n = 167; bortezomib as before plus oral melphalan 9 mg/m(2) and oral prednisone 60 mg/m(2), days 1 to 4, every other cycle), followed by 25 weeks (five 35-day cycles) of bortezomib maintenance (1.6 mg/m(2), days 1, 8, 15, and 22). The primary end point was progression-free survival.
RESULTS: After 42.7 months' median follow-up, median progression-free survival with VD, VTD, and VMP was 14.7, 15.4, and 17.3 months, respectively; median overall survival was 49.8, 51.5, and 53.1 months, with no significant differences among treatments for either end point (global P = .46 and P = .79, respectively, Wald test). Overall response rates were 73% (VD), 80% (VTD), and 70% (VMP). Adverse events were more common with VTD than VD or VMP. Bortezomib maintenance was feasible without producing cumulative toxicity.
CONCLUSION: Although all bortezomib-containing regimens produced good outcomes, VTD and VMP did not appear to offer an advantage over VD in transplantation-ineligible patients with myeloma treated in US community practice.
|Alternate Journal||J. Clin. Oncol.|