TY - JOUR
T1 - Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma
T2 - A multicentre, randomised, double-blind phase 3 trial
AU - San-Miguel, Jesús F.
AU - Hungria, Vânia T M
AU - Yoon, Sung Soo
AU - Beksac, Meral
AU - Dimopoulos, Meletios Athanasios
AU - Elghandour, Ashraf
AU - Jedrzejczak, Wieslaw Wiktor
AU - Günther, Andreas
AU - Nakorn, Thanyaphong Na
AU - Siritanaratkul, Noppadol
AU - Corradini, Paolo
AU - Chuncharunee, Suporn
AU - Lee, Je Jung
AU - Schlossman, Robert L.
AU - Shelekhova, Tatiana
AU - Yong, Kwee
AU - Tan, Daryl
AU - Numbenjapon, Tontanai
AU - Cavenagh, Jamie D.
AU - Hou, Jian
AU - LeBlanc, Richard
AU - Nahi, Hareth
AU - Qiu, Lugui
AU - Salwender, Hans
AU - Pulini, Stefano
AU - Moreau, Philippe
AU - Warzocha, Krzysztof
AU - White, Darrell
AU - Bladé, Joan
AU - Chen, WenMing
AU - de la Rubia, Javier
AU - Gimsing, Peter
AU - Lonial, Sagar
AU - Kaufman, Jonathan L.
AU - Ocio, Enrique M.
AU - Veskovski, Ljupco
AU - Sohn, Sang Kyun
AU - Wang, Ming Chung
AU - Lee, Jae Hoon
AU - Einsele, Hermann
AU - Sopala, Monika
AU - Corrado, Claudia
AU - Bengoudifa, Bourras Rezki
AU - Binlich, Florence
AU - Richardson, Paul G.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - Background: Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Methods: PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1·3 mg/m2 on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators' assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308. Findings: 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6·47 months (IQR 1·81-13·47) in the panobinostat group and 5·59 months (2·14-11·30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11·99 months [95% CI 10·33-12·94] vs 8·08 months [7·56-9·23]; hazard ratio [HR] 0·63, 95% CI 0·52-0·76; p
AB - Background: Panobinostat is a potent oral pan-deacetylase inhibitor that in preclinical studies has synergistic anti-myeloma activity when combined with bortezomib and dexamethasone. We aimed to compare panobinostat, bortezomib, and dexamethasone with placebo, bortezomib, and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Methods: PANORAMA1 is a multicentre, randomised, placebo-controlled, double-blind phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma who have received between one and three previous treatment regimens. Patients were randomly assigned (1:1) via an interactive web-based and voice response system, stratified by number of previous treatment lines and by previous use of bortezomib, to receive 21 day cycles of placebo or panobinostat (20 mg; on days 1, 3, 5, 8, 10, 12, orally), both in combination with bortezomib (1·3 mg/m2 on days 1, 4, 8, 11, intravenously) and dexamethasone (20 mg on days 1, 2, 4, 5, 8, 9, 11, 12, orally). Patients, physicians, and the investigators who did the data analysis were masked to treatment allocation; crossover was not permitted. The primary endpoint was progression-free survival (in accordance with modified European Group for Blood and Marrow Transplantation criteria and based on investigators' assessment) and was analysed by intention to treat. The study is ongoing, but no longer recruiting, and is registered at ClinicalTrials.gov, number NCT01023308. Findings: 768 patients were enrolled between Jan 21, 2010, and Feb 29, 2012, with 387 randomly assigned to panobinostat, bortezomib, and dexamethasone and 381 to placebo, bortezomib, and dexamethasone. Median follow-up was 6·47 months (IQR 1·81-13·47) in the panobinostat group and 5·59 months (2·14-11·30) in the placebo group. Median progression-free survival was significantly longer in the panobinostat group than in the placebo group (11·99 months [95% CI 10·33-12·94] vs 8·08 months [7·56-9·23]; hazard ratio [HR] 0·63, 95% CI 0·52-0·76; p
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U2 - 10.1016/S1470-2045(14)70440-1
DO - 10.1016/S1470-2045(14)70440-1
M3 - Article
C2 - 25242045
AN - SCOPUS:84908133944
VL - 15
SP - 1195
EP - 1206
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 11
ER -