Scientific publications

Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial

San-Miguel JF (1), Hungria VTM (2), Yoon SS (3), Beksac M (4), Dimopoulos MA (5), Elghandour A (6), Jedrzejczak WW (7), Guenther A (8), Na Nakorn T (9), Siritanaratkul N (10), Schlossman RL (11), Hou J (12), Moreau P (13), Lonial S (14), Lee JH (15), Einsele H (16), Salwender H (17), Sopala M (18), Redhu S (19), Paul S (19), Corrado C (18), Richardson PG (11). (1) Clínica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spain.
(2) Santa Casa de Misericordia de São Paulo Hospital, São Paulo, Brazil.
(3) Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
(4) Department of Haematology, Ankara University Faculty of Medicine, Ankara, Turkey.
(5) National and Kapodistrian University of Athens, Athens, Greece.
(6) Alexandria University, Alexandria, Egypt.
(7) Haematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
(8) Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, University Hospital Schleswig-Holstein and University of Kiel, Kiel, Germany.
(9) King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand.
(10) Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
(11) Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
(12) Department of Haematology, Shanghai Changzheng Hospital, Shanghai, China.
(13) University Hospital of Nantes, Nantes, France.
(14) Winship Cancer Institute, Emory University, Atlanta, GA, USA.
(15) Department of Internal Medicine, Gachon University Gil Hospital, Incheon, South Korea.
(16) Medizinische Klinik and Poliklinik II, University of Würzburg, Würzburg, Germany.
(17) Asklepios Klinik Altona, Hamburg, Germany.
(18) Novartis Pharma AG, Basel, Switzerland.
(19) Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Magazine: British Journal of Haematology

Date: Jun 27, 2017

Hematología y Hemoterapia [SP]

ABSTRACT

Panobinostat in combination with bortezomib and dexamethasone demonstrated a significant and clinically meaningful progression-free survival benefit compared with placebo, bortezomib and dexamethasone in the phase 3 PANORAMA 1 (Panobinostat Oral in Multiple Myeloma 1) trial.

Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (AEs) and higher rates of discontinuation due to AEs. This PANORAMA 1 subanalysis examined AEs between 2 treatment phases of the study (TP1 and TP2), in which administration frequency of bortezomib and dexamethasone differed per protocol.

The incidences of several key AEs were lower in both arms following the planned reduction of bortezomib dosing frequency in TP2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP1, 56·7%; TP2, 6·0%), diarrhoea (grade 3/4: TP1, 24·1%; TP2, 7·1%), and fatigue (grade 3/4: TP1, 16·3%; TP2, 1·8%) were lower in TP2 compared with TP1.

Dose intensity analysis of panobinostat and bortezomib by cycle in the panobinostat arm showed reductions of both agent doses during cycles 1-4 due to dose adjustments for AEs. Exposure-adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP1 following dose adjustment.

These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes.

CITATON  Br J Haematol. 2017 Jun 27. doi: 10.1111/bjh.14821

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