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.
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.
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.
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.
gov registration number: NCT02987543.
European journal of cancer (Oxford, England : 1990). 2022 May 18 [Epub ahead of print]
Guilhem Roubaud, Mustafa Özgüroğlu, Nicolas Penel, Nobuaki Matsubara, Niven Mehra, Michael P Kolinsky, Giuseppe Procopio, Susan Feyerabend, Jae Young Joung, Gwenaelle Gravis, Kazuo Nishimura, Craig Gedye, Charles Padua, Neal Shore, Antoine Thiery-Vuillemin, Fred Saad, Robbert van Alphen, Michael A Carducci, Chintu Desai, Neil Brickel, Christian Poehlein, Paula Del Rosario, Karim Fizazi
Department of Medical Oncology, Institut Bergonié, Bordeaux, France. Electronic address: ., Department of Internal Medicine, Division of Medical Oncology, Cerrahpaşa School of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey., Lille University and Centre Oscar Lambret, Lille, France., National Cancer Center Hospital East, Chiba, Japan., Radboud University Medical Center, Nijmegen, the Netherlands., Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada., Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy., Urologic Oncology, Studienpraxis Urologie, Nürtingen, Germany., Center for Prostate Cancer, National Cancer Center, Goyang, South Korea., Institut Paoli-Calmettes, Marseilles, France., Department of Urology, Osaka International Cancer Institute, Osaka, Japan., Calvary Mater Newcastle, Waratah, Australia., Cetus Medicina Oncológica, Betim, Brazil., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Medical Oncology Unit, CHU Besançon, Besançon, France., Centre Hospitalier de L'Universite de Montreal, Montreal, Canada., Elisabeth-Tweesteden Ziekenhuis, Tilburg, the Netherlands., Hopkins Kimmel Cancer Center, Maryland, USA., AstraZeneca, Cambridge, UK., Merck & Co., Inc., Kenilworth, NJ, USA., Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.