Ruben Niesvizky1, Ian W Flinn2, Robert Rifkin2, Nashat Gabrail2, Veena Charu2, Billy Clowney2, James Essell2, Yousuf Gaffar2, Thomas Warr2, Rachel Neuwirth2, Yanyan Zhu2, Jennifer Elliott2, Dixie-Lee Esseltine2, Liviu Niculescu2, James Reeves2. 1. Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL. run9001@med.cornell.edu. 2. Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
Abstract
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.
RCT Entities:
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.
Authors: Elizabeth K O'Donnell; Jacob P Laubach; Andrew J Yee; Tianqi Chen; Carol Ann Huff; Frank G Basile; Philip M Wade; Claudia E Paba-Prada; Irene M Ghobrial; Robert L Schlossman; Jill N Burke; Cynthia C Harrington; Kathleen J Lively; Hannah F Lyons; Nikhil C Munshi; Kenneth C Anderson; Lorenzo Trippa; Paul G Richardson; Noopur S Raje Journal: Br J Haematol Date: 2018-05-08 Impact factor: 6.998