@article{3087647,
    title = "Continuous therapy versus fixed duration of therapy in patients with newly diagnosed multiple myeloma",
    author = "Palumbo, A. and Gay, F. and Cavallo, F. and Raimondo, F.D. and Larocca, A. and Hardan, I. and Nagler, A. and Petrucci, M.T. and Hajek, R. and Pezzatti, S. and Delforge, M. and Patriarca, F. and Donato, F. and Cerrato, C. and Nozzoli, C. and Yu, Z. and Boccadifuoco, L. and Caravita, T. and Benevolo, G. and Guglielmelli, T. and Vincelli, D. and Jacques, C. and Dimopoulos, M.A. and Ciccone, G. and Musto, P. and Corradini, P. and Cavo, M. and Boccadoro, M.",
    journal = "Journal of Clinical Oncology",
    year = "2015",
    volume = "33",
    number = "30",
    pages = "3459-3466",
    publisher = "American Society of Clinical Oncology",
    issn = "0732-183X, 1527-7755",
    doi = "10.1200/JCO.2014.60.2466",
    keywords = "bortezomib;  lenalidomide;  thalidomide;  antineoplastic agent;  bortezomib;  dexamethasone;  lenalidomide;  melphalan;  prednisone;  thalidomide, adult;  aged;  Article;  cancer combination chemotherapy;  cancer recurrence;  continuous therapy;  female;  fixed duration of therapy;  follow up;  human;  intention to treat analysis;  major clinical study;  male;  multiple myeloma;  overall survival;  phase 3 clinical trial (topic);  post treatment survival;  priority journal;  progression free survival;  randomized controlled trial (topic);  treatment duration;  analogs and derivatives;  clinical trial;  controlled study;  disease free survival;  drug administration;  middle aged;  multiple myeloma;  phase 3 clinical trial;  randomized controlled trial, Aged;  Antineoplastic Combined Chemotherapy Protocols;  Bortezomib;  Dexamethasone;  Disease-Free Survival;  Drug Administration Schedule;  Female;  Humans;  Male;  Melphalan;  Middle Aged;  Multiple Myeloma;  Prednisone;  Thalidomide",
    abstract = "Purpose: Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy-resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent-based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma. Methods: We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent-based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models. Results: In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P < .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P < .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003). Conclusion: In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials. Copyright © 2015 American Society of Clinical Oncology. All rights reserved."
}