Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial.
San-Miguel JF (1), Hungria VT (2), Yoon SS (3), Beksac M (4), Dimopoulos MA (5), Elghandour A (6), Jedrzejczak WW (7), Günther A (8), Nakorn TN (9), Siritanaratkul N (10), Schlossman RL (11), Hou J (12), Moreau P (13), Lonial S (14), Lee JH (15), Einsele H (16), Sopala M (17), Bengoudifa BR (17), Binlich F (18), Richardson PG (11).
(1) Clínica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain.
(2) Irmandade da Santa Casa de Misericordia de São Paulo, São Paulo, Brazil.
(3) Seoul National University Hospital, Seoul, South Korea.
(4) Ankara University School of Medicine, Ankara, Turkey.
(5) National and Kapodistrian University of Athens, Athens, Greece.
(6) Alexandria University, Alexandria, Egypt.
(7) Medical University of Warsaw, Warsaw, Poland.
(8) University of Kiel, Kiel, Germany.
(9) King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand.
(10) Siriraj Hospital, Bangkok, Thailand.
(11) Dana-Farber Cancer Institute, Boston, MA, USA.
(12) Shanghai Changzheng Hospital, Shanghai, China.
13University Hospital of Nantes, Nantes, France.
14Winship Cancer Institute of Emory University, Atlanta, GA, USA.
15Gachon University Gil Medical Center, Incheon, South Korea.
16University Hospital Würzburg, Würzburg, Germany.
17Novartis Pharma AG, Basel, Switzerland.
18Novartis Pharma SAS, Rueil-Malmaison, France.
Revisão:The Lancet. Haematology
Data: 14/Out/2016Hematologia e Hemoterapia
Panobinostat plus bortezomib and dexamethasone significantly increased median progression-free survival compared with placebo plus bortezomib and dexamethasone in the phase 3 PANORAMA 1 trial. Here, we present the final overall survival analysis for this trial.
PANORAMA 1 is a randomised, placebo-controlled, double-blind, phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma with one to three previous treatments.
Patients were randomly assigned (1:1) to receive panobinostat (20 mg orally) or placebo, with bortezomib (1·3 mg/m2 intravenously) and dexamethasone (20 mg orally), over two distinct treatment phases. In treatment phase 1 (eight 3-week cycles), patients received: panobinostat or placebo on days 1, 3, 5, 8, 10, and 12; bortezomib on days 1, 4, 8, and 11; and dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12.
During treatment phase 2 (four 6-week cycles with a 2 weeks on, 1 week off schedule), panobinostat or placebo was given three times a week, bortezomib was administered once a week, and dexamethasone was given on the days of and following bortezomib administration. The primary endpoint was progression-free survival; overall survival was a key secondary endpoint. This study is registered at ClinicalTrials.gov, NCT01023308.
Between Jan 21, 2010, and Feb 29, 2012, 768 patients were enrolled into the study and randomly assigned to receive either panobinostat (n=387) or placebo (n=381), plus bortezomib and dexamethasone. At data cutoff (June 29, 2015), 415 patients had died.
Median overall survival was 40·3 months (95% CI 35·0-44·8) in those who received panobinostat, bortezomib, and dexamethasone versus 35·8 months (29·0-40·6) in those who received placebo, bortezomib, and dexamethasone (hazard ratio [HR] 0·94, 95% CI 0·78-1·14; p=0·54).
Of patients who had received at least two previous regimens including bortezomib and an immunomodulatory drug, median overall survival was 25·5 months (95% CI 19·6-34·3) in 73 patients who received panobinostat, bortezomib, and dexamethasone versus 19·5 months (14·1-32·5) in 74 who received placebo (HR 1·01, 95% CI 0·68-1·50).
The overall survival benefit with panobinostat over placebo with bortezomib and dexamethasone was modest. However, optimisation of the regimen could potentially prolong treatment duration and improve patients' outcomes, although further trials will be required to confirm this.
CITAÇÃO DO ARTIGO Lancet Haematol. 2016 Oct 14. pii: S2352-3026(16)30147-8. doi: 10.1016/S2352-3026(16)30147-8.
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