PMID- 27358383 OWN - NLM STAT- MEDLINE DCOM- 20180102 LR - 20220331 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 27 IP - 9 DP - 2016 Sep TI - Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). PG - 1719-25 LID - 10.1093/annonc/mdw249 [doi] AB - 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. CI - (c) The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Jerusalem, G AU - Jerusalem G AD - Department of Medical Oncology, CHU Sart Tilman Liege and Liege University, Domaine Universitaire du Sart Tilman, Liege, Belgium g.jerusalem@chu.ulg.ac.be. FAU - Mariani, G AU - Mariani G AD - Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. FAU - Ciruelos, E M AU - Ciruelos EM AD - Medical Oncology Department, Breast Cancer Unit, University Hospital 12 de Octubre, Madrid, Spain. FAU - Martin, M AU - Martin M AD - Instituto de Investigacion Sanitaria Gregorio Maranon, Univesidad Complutense, Madrid, Spain. FAU - Tjan-Heijnen, V C G AU - Tjan-Heijnen VC AD - Department of Medical Oncology, GROW, Maastricht University Medical Centre, Maastricht, The Netherlands. FAU - Neven, P AU - Neven P AD - KULeuven (University of Leuven), Department of Oncology, Multidisciplinary Breast Center, University Hospitals Leuven, Belgium. FAU - Gavila, J G AU - Gavila JG AD - Medical Oncology Unit of Fundacion Instituto Valenciano De Oncologia, Valencia, Spain. FAU - Michelotti, A AU - Michelotti A AD - UO Oncologia Medica I, Azienda Ospedaliera Universitaria Pisana, Santa Chiara Hospital, Pisa, Italy. FAU - Montemurro, F AU - Montemurro F AD - Unit of Investigative Clinical Oncology (INCO), Fondazione del Piemonte per l'Oncologia, Institute of Candiolo Cancer Center (IRCCs), Candiolo, Torino, Italy. FAU - Generali, D AU - Generali D AD - Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy. FAU - Simoncini, E AU - Simoncini E AD - Breast Unit, Azienda Ospedaliera Spedali Civili, Brescia, Italy. FAU - Lang, I AU - Lang I AD - Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary. FAU - Mardiak, J AU - Mardiak J AD - Narodny Onkologicky Ustav Klenova 1, Bratislava, Slovakia. FAU - Naume, B AU - Naume B AD - 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. FAU - Camozzi, M AU - Camozzi M AD - Novartis Farma S.p.A., Origgio, VA, Italy. FAU - Lorizzo, K AU - Lorizzo K AD - Novartis Farma S.p.A., Origgio, VA, Italy. FAU - Bianchetti, S AU - Bianchetti S AD - Novartis Farma S.p.A., Origgio, VA, Italy. FAU - Conte, P AU - Conte P AD - Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy Medical Oncology 2, Istituto Oncologico Veneto, Padova, Italy. LA - eng SI - EudraCT/2012-000073-23 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study DEP - 20160629 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Androstadienes) RN - 0 (Aromatase Inhibitors) RN - 0 (Receptors, Estrogen) RN - 9HW64Q8G6G (Everolimus) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - NY22HMQ4BX (exemestane) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Aged MH - Aged, 80 and over MH - Androstadienes/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects MH - Aromatase Inhibitors/administration & dosage/adverse effects MH - Breast Neoplasms/*drug therapy/genetics/pathology MH - Disease-Free Survival MH - Drug-Related Side Effects and Adverse Reactions/classification/pathology MH - ErbB Receptors/genetics MH - Everolimus/*administration & dosage/adverse effects MH - Female MH - Humans MH - Male MH - Neoplasm Metastasis MH - Neoplasm Recurrence, Local/*drug therapy/genetics/pathology MH - Postmenopause MH - Receptor, ErbB-2/genetics MH - Receptors, Estrogen/genetics MH - Sirolimus OTO - NOTNLM OT - BMI OT - advanced breast cancer OT - elderly OT - everolimus OT - hormone-receptor positive OT - stomatitis EDAT- 2016/07/01 06:00 MHDA- 2018/01/03 06:00 CRDT- 2016/07/01 06:00 PHST- 2016/02/05 00:00 [received] PHST- 2016/06/13 00:00 [accepted] PHST- 2016/07/01 06:00 [entrez] PHST- 2016/07/01 06:00 [pubmed] PHST- 2018/01/03 06:00 [medline] AID - S0923-7534(19)35877-6 [pii] AID - 10.1093/annonc/mdw249 [doi] PST - ppublish SO - Ann Oncol. 2016 Sep;27(9):1719-25. doi: 10.1093/annonc/mdw249. Epub 2016 Jun 29.