G Jerusalem1, G Mariani2, E M Ciruelos3, M Martin4, V C G Tjan-Heijnen5, P Neven6, J G Gavila7, A Michelotti8, F Montemurro9, D Generali10, E Simoncini11, I Lang12, J Mardiak13, B Naume14, M Camozzi15, K Lorizzo15, S Bianchetti15, P Conte16. 1. Department of Medical Oncology, CHU Sart Tilman Liege and Liege University, Domaine Universitaire du Sart Tilman, Liege, Belgium g.jerusalem@chu.ulg.ac.be. 2. Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. 3. Medical Oncology Department, Breast Cancer Unit, University Hospital 12 de Octubre, Madrid, Spain. 4. Instituto de Investigación Sanitaria Gregorio Marañón, Univesidad Complutense, Madrid, Spain. 5. Department of Medical Oncology, GROW, Maastricht University Medical Centre, Maastricht, The Netherlands. 6. KULeuven (University of Leuven), Department of Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, Belgium. 7. Medical Oncology Unit of Fundacion Instituto Valenciano De Oncologia, Valencia, Spain. 8. UO Oncologia Medica I, Azienda Ospedaliera Universitaria Pisana, Santa Chiara Hospital, Pisa, Italy. 9. Unit of Investigative Clinical Oncology (INCO), Fondazione del Piemonte per l'Oncologia, Institute of Candiolo Cancer Center (IRCCs), Candiolo, Torino, Italy. 10. Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy. 11. Breast Unit, Azienda Ospedaliera Spedali Civili, Brescia, Italy. 12. Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary. 13. Narodny Onkologicky Ustav Klenova 1, Bratislava, Slovakia. 14. Department of Oncology, Oslo University Hospital, Oslo, Norway K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 15. Novartis Farma S.p.A., Origgio, VA, Italy. 16. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy Medical Oncology 2, Istituto Oncologico Veneto, Padova, Italy.
Abstract
BACKGROUND: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. PATIENTS AND METHODS: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. RESULTS: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. CONCLUSIONS: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2012-000073-23.
BACKGROUND: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. PATIENTS AND METHODS: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. RESULTS: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. CONCLUSIONS: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2012-000073-23.
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Authors: Guy Jerusalem; Richard H de Boer; Sara Hurvitz; Denise A Yardley; Elena Kovalenko; Bent Ejlertsen; Sibel Blau; Mustafa Özgüroglu; László Landherr; Marianne Ewertz; Tetiana Taran; Jenna Fan; Florence Noel-Baron; Anne-Laure Louveau; Howard Burris Journal: JAMA Oncol Date: 2018-10-01 Impact factor: 31.777
Authors: Tomas Pascual; María Apellániz-Ruiz; Cristina Pernaut; Cecilia Cueto-Felgueroso; Pablo Villalba; Carlos Álvarez; Luis Manso; Lucia Inglada-Pérez; Mercedes Robledo; Cristina Rodríguez-Antona; Eva Ciruelos Journal: PLoS One Date: 2017-07-20 Impact factor: 3.240