Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens.

TitleCommunity-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens.
Publication TypeJournal Article
Year of Publication2015
AuthorsNiesvizky 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
JournalJ Clin Oncol
Date Published2015 Nov 20
KeywordsAdrenal 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 JournalJ. Clin. Oncol.
PubMed ID26056177