PMID- 28653400 OWN - NLM STAT- MEDLINE DCOM- 20171009 LR - 20181202 IS - 1365-2141 (Electronic) IS - 0007-1048 (Linking) VI - 179 IP - 1 DP - 2017 Oct TI - Panobinostat plus bortezomib and dexamethasone: impact of dose intensity and administration frequency on safety in the PANORAMA 1 trial. PG - 66-74 LID - 10.1111/bjh.14821 [doi] AB - 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. CI - (c) 2017 John Wiley & Sons Ltd. FAU - San-Miguel, Jesus F AU - San-Miguel JF AUID- ORCID: 0000-0002-9183-4857 AD - Clinica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spain. FAU - Hungria, Vania T M AU - Hungria VTM AD - Santa Casa de Misericordia de Sao Paulo Hospital, Sao Paulo, Brazil. FAU - Yoon, Sung-Soo AU - Yoon SS AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. FAU - Beksac, Meral AU - Beksac M AD - Department of Haematology, Ankara University Faculty of Medicine, Ankara, Turkey. FAU - Dimopoulos, Meletios A AU - Dimopoulos MA AUID- ORCID: 0000-0001-8990-3254 AD - National and Kapodistrian University of Athens, Athens, Greece. FAU - Elghandour, Ashraf AU - Elghandour A AD - Alexandria University, Alexandria, Egypt. FAU - Jedrzejczak, Wieslaw W AU - Jedrzejczak WW AD - Haematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland. FAU - Guenther, Andreas AU - Guenther A AD - Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, University Hospital Schleswig-Holstein and University of Kiel, Kiel, Germany. FAU - Na Nakorn, Thanyaphong AU - Na Nakorn T AD - King Chulalongkorn Memorial Hospital and Chulalongkorn University, Bangkok, Thailand. FAU - Siritanaratkul, Noppadol AU - Siritanaratkul N AD - Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. FAU - Schlossman, Robert L AU - Schlossman RL AD - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. FAU - Hou, Jian AU - Hou J AD - Department of Haematology, Shanghai Changzheng Hospital, Shanghai, China. FAU - Moreau, Philippe AU - Moreau P AUID- ORCID: 0000-0003-1780-8746 AD - University Hospital of Nantes, Nantes, France. FAU - Lonial, Sagar AU - Lonial S AD - Winship Cancer Institute, Emory University, Atlanta, GA, USA. FAU - Lee, Jae-Hoon AU - Lee JH AD - Department of Internal Medicine, Gachon University Gil Hospital, Incheon, South Korea. FAU - Einsele, Hermann AU - Einsele H AUID- ORCID: 0000-0002-7680-0819 AD - Medizinische Klinik and Poliklinik II, University of Wurzburg, Wurzburg, Germany. FAU - Salwender, Hans AU - Salwender H AD - Asklepios Klinik Altona, Hamburg, Germany. FAU - Sopala, Monika AU - Sopala M AD - Novartis Pharma AG, Basel, Switzerland. FAU - Redhu, Suman AU - Redhu S AD - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. FAU - Paul, Sofia AU - Paul S AD - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. FAU - Corrado, Claudia AU - Corrado C AD - Novartis Pharma AG, Basel, Switzerland. FAU - Richardson, Paul G AU - Richardson PG AD - Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20170627 PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (Hydroxamic Acids) RN - 0 (Indoles) RN - 69G8BD63PP (Bortezomib) RN - 7S5I7G3JQL (Dexamethasone) RN - 9647FM7Y3Z (Panobinostat) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Bortezomib/administration & dosage MH - Combined Modality Therapy MH - Dexamethasone/administration & dosage MH - Disease Progression MH - Drug Administration Schedule MH - Drug Resistance, Neoplasm MH - Female MH - Hematopoietic Stem Cell Transplantation MH - Humans MH - Hydroxamic Acids/administration & dosage MH - Indoles/administration & dosage MH - Male MH - Middle Aged MH - Multiple Myeloma/*drug therapy/pathology MH - Panobinostat MH - Recurrence MH - Transplantation, Autologous MH - Treatment Outcome OTO - NOTNLM OT - deacetylase inhibitor OT - dose intensity OT - multiple myeloma OT - panobinostat OT - safety EDAT- 2017/06/28 06:00 MHDA- 2017/10/11 06:00 CRDT- 2017/06/28 06:00 PHST- 2017/03/21 00:00 [received] PHST- 2017/05/15 00:00 [accepted] PHST- 2017/06/28 06:00 [pubmed] PHST- 2017/10/11 06:00 [medline] PHST- 2017/06/28 06:00 [entrez] AID - 10.1111/bjh.14821 [doi] PST - ppublish SO - Br J Haematol. 2017 Oct;179(1):66-74. doi: 10.1111/bjh.14821. Epub 2017 Jun 27.