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BIBTEX RIS

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

2017; Wiley; Volume: 179; Issue: 1 Linguagem: Inglês

10.1111/bjh.14821

ISSN

1365-2141

Autores

Jesús F. San Miguel, Vânia Hungria, Sung‐Soo Yoon, Meral Beksaç, Meletios Α. Dimopoulos, Ashraf Elghandour, W Wiktor-Jędrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Hans Salwender, Monika Sopala, Suman Redhu, Sofia Paul, Claudia Corrado, Paul G. Richardson,

Tópico(s)

Protein Degradation and Inhibitors

Resumo

Summary 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 ( AE s) and higher rates of discontinuation due to AE s. This PANORAMA 1 subanalysis examined AE s between 2 treatment phases of the study ( TP 1 and TP 2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key AE s were lower in both arms following the planned reduction of bortezomib dosing frequency in TP 2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: TP 1, 56·7%; TP 2, 6·0%), diarrhoea (grade 3/4: TP 1, 24·1%; TP 2, 7·1%), and fatigue (grade 3/4: TP 1, 16·3%; TP 2, 1·8%) were lower in TP 2 compared with TP 1. 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 AE s. Exposure‐adjusted analysis demonstrated a reduction in thrombocytopenia frequency in TP 1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes.

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