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.

Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma

PALUMBO, Antonio
First
;
GAY, Francesca Maria;CAVALLO, Federica;LAROCCA, Alessandra;Donato, Francesca;CERRATO, CHIARA;BOCCADORO, Mario
Last
2015-01-01

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.
2015
33
30
3459
3466
https://ascopubs.org/doi/10.1200/JCO.2014.60.2466
https://doi.org/10.1200/jco.2014.60.2466
Palumbo, Antonio; Gay, Francesca; Cavallo, Federica; Di Raimondo, Francesco; Larocca, Alessandra; Hardan, Izhar; Nagler, Arnon; Petrucci, Maria T; Hajek, Roman; Pezzatti, Sara; Delforge, Michel; Patriarca, Francesca; Donato, Francesca; Cerrato, Chiara; Nozzoli, Chiara; Yu, Zhinuan; Boccadifuoco, Luana; Caravita, Tommaso; Benevolo, Giulia; Guglielmelli, Tommasina; Vincelli, Donatella; Jacques, Christian; Dimopoulos, Meletios A; Ciccone, Giovannino; Musto, Pellegrino; Corradini, Paolo; Cavo, Michele; Boccadoro, Mario
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Descrizione: Restricted access - Published version and Appendix. Palumbo A, Gay F, Cavallo F, Di Raimondo F, Larocca A, Hardan I, Nagler A, Petrucci MT, 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 MA, Ciccone G, Musto P, Corradini P, Cavo M, Boccadoro M. Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2015 Oct 20;33(30):3459-66. doi: 10.1200/JCO.2014.60.2466. Epub 2015 Aug 17. PMID: 26282661. © 2015 by American Society of Clinical Oncology. Available at: https://ascopubs.org/doi/pdf/10.1200/JCO.2014.60.2466?role=tab | https://doi.org/10.1200/jco.2014.60.2466
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[Author Vsn and Appendix] Palumbo et al - 2015 - JCO - CT vs FDT.pdf

Open Access dal 02/11/2016

Descrizione: Author's version and Appendix. Palumbo A, Gay F, Cavallo F, Di Raimondo F, Larocca A, Hardan I, Nagler A, Petrucci MT, 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 MA, Ciccone G, Musto P, Corradini P, Cavo M, Boccadoro M. Continuous Therapy Versus Fixed Duration of Therapy in Patients With Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2015 Oct 20;33(30):3459-66. doi: 10.1200/JCO.2014.60.2466. Epub 2015 Aug 17. PMID: 26282661. © 2015 by American Society of Clinical Oncology. Available at: https://ascopubs.org/doi/pdf/10.1200/JCO.2014.60.2466?role=tab | https://doi.org/10.1200/jco.2014.60.2466 . When citing, please refer to the published version.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1526942
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