Τίτλος:
Continuous therapy versus fixed duration of therapy in patients with newly diagnosed multiple myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Palumbo, A.
Gay, F.
Cavallo, F.
Raimondo, F.D.
Larocca, A.
Hardan, I.
Nagler, A.
Petrucci, M.T.
Hajek, R.
Pezzatti, S.
Delforge, M.
Patriarca, F.
Donato, F.
Cerrato, C.
Nozzoli, C.
Yu, Z.
Boccadifuoco, L.
Caravita, T.
Benevolo, G.
Guglielmelli, T.
Vincelli, D.
Jacques, C.
Dimopoulos, M.A.
Ciccone, G.
Musto, P.
Corradini, P.
Cavo, M.
Boccadoro, M.
Περιοδικό:
Journal of Clinical Oncology
Εκδότης:
American Society of Clinical Oncology
Λέξεις-κλειδιά:
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
DOI:
10.1200/JCO.2014.60.2466
