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Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial
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Titel: |
Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial |
In: | British Journal of Haematology, 179, 2017, 1, S. 66-74 |
veröffentlicht: |
Wiley
|
Umfang: | 66-74 |
ISSN: |
0007-1048 1365-2141 |
DOI: | 10.1111/bjh.14821 |
Zusammenfassung: | <jats:title>Summary</jats:title><jats:p>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 <jats:styled-content style="fixed-case">PANORAMA</jats:styled-content> 1 (Panobinostat Oral in Multiple Myeloma 1) trial. Despite this benefit, patients in the panobinostat arm experienced higher rates of adverse events (<jats:styled-content style="fixed-case">AE</jats:styled-content>s) and higher rates of discontinuation due to <jats:styled-content style="fixed-case">AE</jats:styled-content>s. This <jats:styled-content style="fixed-case">PANORAMA</jats:styled-content> 1 subanalysis examined <jats:styled-content style="fixed-case">AE</jats:styled-content>s between 2 treatment phases of the study (<jats:styled-content style="fixed-case">TP</jats:styled-content>1 and <jats:styled-content style="fixed-case">TP</jats:styled-content>2), in which administration frequency of bortezomib and dexamethasone differed per protocol. The incidences of several key <jats:styled-content style="fixed-case">AE</jats:styled-content>s were lower in both arms following the planned reduction of bortezomib dosing frequency in <jats:styled-content style="fixed-case">TP</jats:styled-content>2. In the panobinostat arm, rates of thrombocytopenia (grade 3/4: <jats:styled-content style="fixed-case">TP</jats:styled-content>1, 56·7%; <jats:styled-content style="fixed-case">TP</jats:styled-content>2, 6·0%), diarrhoea (grade 3/4: <jats:styled-content style="fixed-case">TP</jats:styled-content>1, 24·1%; <jats:styled-content style="fixed-case">TP</jats:styled-content>2, 7·1%), and fatigue (grade 3/4: <jats:styled-content style="fixed-case">TP</jats:styled-content>1, 16·3%; <jats:styled-content style="fixed-case">TP</jats:styled-content>2, 1·8%) were lower in <jats:styled-content style="fixed-case">TP</jats:styled-content>2 compared with <jats:styled-content style="fixed-case">TP</jats:styled-content>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 <jats:styled-content style="fixed-case">AE</jats:styled-content>s. Exposure‐adjusted analysis demonstrated a reduction in thrombocytopenia frequency in <jats:styled-content style="fixed-case">TP</jats:styled-content>1 following dose adjustment. These results suggest that optimization of dosing with this regimen could improve tolerability, potentially leading to improved patient outcomes.</jats:p> |
Format: | E-Article |
Quelle: | Wiley (CrossRef) |
Sprache: | Englisch |