PMID- 35598359 OWN - NLM STAT- MEDLINE DCOM- 20220628 LR - 20220702 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 170 DP - 2022 Jul TI - Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study. PG - 73-84 LID - S0959-8049(22)00217-9 [pii] LID - 10.1016/j.ejca.2022.04.016 [doi] AB - BACKGROUND: Based on PROfound, olaparib is approved for patients with metastatic castration-resistant prostate cancer following disease progression on at least enzalutamide or abiraterone and who carry relevant alterations in DNA repair genes. To facilitate continued olaparib treatment as long as the patient derives benefit, we describe further safety assessments from PROfound focusing on the four most common adverse events (AEs) and events of special interest. METHODS: Patients were randomized (2:1) to olaparib tablets (300 mg bid) or control (enzalutamide or abiraterone) until disease progression or unacceptable toxicity. Safety was assessed through AE reporting and laboratory assessments. Safety data were also collected from all patients in the control group who experienced radiographic disease progression and subsequently crossed over to olaparib treatment. RESULTS: 256 patients received olaparib and 130 control. Incidence rates for the four most commonly occurring AEs in the olaparib group (all-causality) were anaemia 50%, nausea 43%, fatigue/asthenia 42% and decreased appetite 31%. All were mostly Grade 1 and 2 and all peaked within the first 2 months of treatment as the events were managed where appropriate, primarily with dose interruptions or dose reductions. The extent of bone metastases at baseline or prior taxane use was not associated with the rate of anaemia. Pneumonitis was reported in 2% and 1.5% of patients in the olaparib and control groups, respectively, and one patient (0.4%) in the olaparib group experienced an event of MDS/AML after a 30-day follow-up period. Venous thromboembolic events occurred in 8% of olaparib and 3% of control patients. CONCLUSIONS: The four most common AEs observed in PROfound were generally manageable without the need for treatment discontinuation, allowing patients to remain on treatment for as long as they were deriving clinical benefit. CLINICALTRIALS: gov registration number: NCT02987543. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Roubaud, Guilhem AU - Roubaud G AD - Department of Medical Oncology, Institut Bergonie, Bordeaux, France. Electronic address: G.Roubaud@bordeaux.unicancer.fr. FAU - Ozguroglu, Mustafa AU - Ozguroglu M AD - Department of Internal Medicine, Division of Medical Oncology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey. FAU - Penel, Nicolas AU - Penel N AD - Lille University and Centre Oscar Lambret, Lille, France. FAU - Matsubara, Nobuaki AU - Matsubara N AD - National Cancer Center Hospital East, Chiba, Japan. FAU - Mehra, Niven AU - Mehra N AD - Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Kolinsky, Michael P AU - Kolinsky MP AD - Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Procopio, Giuseppe AU - Procopio G AD - Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. FAU - Feyerabend, Susan AU - Feyerabend S AD - Urologic Oncology, Studienpraxis Urologie, Nurtingen, Germany. FAU - Joung, Jae Young AU - Joung JY AD - Center for Prostate Cancer, National Cancer Center, Goyang, South Korea. FAU - Gravis, Gwenaelle AU - Gravis G AD - Institut Paoli-Calmettes, Marseilles, France. FAU - Nishimura, Kazuo AU - Nishimura K AD - Department of Urology, Osaka International Cancer Institute, Osaka, Japan. FAU - Gedye, Craig AU - Gedye C AD - Calvary Mater Newcastle, Waratah, Australia. FAU - Padua, Charles AU - Padua C AD - Cetus Medicina Oncologica, Betim, Brazil. FAU - Shore, Neal AU - Shore N AD - Carolina Urologic Research Center, Myrtle Beach, SC, USA. FAU - Thiery-Vuillemin, Antoine AU - Thiery-Vuillemin A AD - Medical Oncology Unit, CHU Besancon, Besancon, France. FAU - Saad, Fred AU - Saad F AD - Centre Hospitalier de L'Universite de Montreal, Montreal, Canada. FAU - van Alphen, Robbert AU - van Alphen R AD - Elisabeth-Tweesteden Ziekenhuis, Tilburg, the Netherlands. FAU - Carducci, Michael A AU - Carducci MA AD - Hopkins Kimmel Cancer Center, Maryland, USA. FAU - Desai, Chintu AU - Desai C AD - AstraZeneca, Cambridge, UK. FAU - Brickel, Neil AU - Brickel N AD - AstraZeneca, Cambridge, UK. FAU - Poehlein, Christian AU - Poehlein C AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Del Rosario, Paula AU - Del Rosario P AD - AstraZeneca, Cambridge, UK. FAU - Fizazi, Karim AU - Fizazi K AD - Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France. LA - eng SI - ClinicalTrials.gov/NCT02987543 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220519 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Phthalazines) RN - 0 (Piperazines) RN - WOH1JD9AR8 (olaparib) SB - IM MH - *Anemia/chemically induced MH - Disease Progression MH - Humans MH - Male MH - Phthalazines/adverse effects MH - Piperazines MH - *Prostatic Neoplasms, Castration-Resistant/pathology OTO - NOTNLM OT - Adverse-event management OT - Metastatic castration-resistant prostate cancer OT - Olaparib OT - PROfound OT - Safety EDAT- 2022/05/23 06:00 MHDA- 2022/06/29 06:00 CRDT- 2022/05/22 18:07 PHST- 2021/12/15 00:00 [received] PHST- 2022/03/24 00:00 [revised] PHST- 2022/04/01 00:00 [accepted] PHST- 2022/05/23 06:00 [pubmed] PHST- 2022/06/29 06:00 [medline] PHST- 2022/05/22 18:07 [entrez] AID - S0959-8049(22)00217-9 [pii] AID - 10.1016/j.ejca.2022.04.016 [doi] PST - ppublish SO - Eur J Cancer. 2022 Jul;170:73-84. doi: 10.1016/j.ejca.2022.04.016. Epub 2022 May 19.