PMID- 28432226 OWN - NLM STAT- MEDLINE DCOM- 20180316 LR - 20220408 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 22 IP - 6 DP - 2017 Jun TI - Everolimus Plus Exemestane in Advanced Breast Cancer: Safety Results of the BALLET Study on Patients Previously Treated Without and with Chemotherapy in the Metastatic Setting. PG - 648-654 LID - 10.1634/theoncologist.2016-0461 [doi] AB - BACKGROUND: The BALLET study was an open-label, multicenter, expanded access study designed to allow treatment with everolimus plus exemestane in postmenopausal women with hormone receptor-positive metastatic breast cancer progressed following prior endocrine therapy. A post hoc analysis to evaluate if previous chemotherapy in the metastatic setting affects the safety profile of the combination regimen of everolimus and exemestane was conducted on the Italian subset, as it represented the major part of the patients enrolled (54%). PATIENTS AND METHODS: One thousand one hundred and fifty-one Italian patients were included in the present post hoc analysis, which focused on two sets of patients: patients who never received chemotherapy in the metastatic setting (36.1%) and patients who received at least one chemotherapy treatment in the metastatic setting (63.9%). RESULTS: One thousand one hundred and sixteen patients (97.0%) prematurely discontinued the study drug, and the main reasons reported were disease progression (39.1%), local reimbursement of everolimus (31.1%), and adverse events (AEs) (16.1%). The median duration of study treatment exposure was 139.5 days for exemestane and 135.0 days for everolimus. At least one AE was experienced by 92.5% of patients. The incidence of everolimus-related AEs was higher (83.9%) when compared with those that occurred with exemestane (29.1%), and the most commonly reported everolimus-related AE was stomatitis (51.3%). However, no significant difference in terms of safety related to the combination occurred between patients without and with chemotherapy in the metastatic setting. CONCLUSION: Real-life data of the Italian patients BALLET-related cohort were an adequate setting to state that previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. IMPLICATIONS FOR PRACTICE: With the advent of new targeted agents for advanced or metastatic breast cancer, multiple lines of therapy may be possible, and components of the combined regimens can overlap from one line to another. Thus, it is important to assess even the potential of cumulative and additive toxic effects among the drugs. Previous chemotherapy did not affect the safety profile of the combination regimen of everolimus and exemestane. The continuous monitoring of the safety signals of this drug combination from general clinical practice is important, in particular for stomatitis. CI - (c) AlphaMed Press 2017. FAU - Generali, Daniele AU - Generali D AD - Breast Cancer Unit and Molecular Therapy Unit, Azienda Socio Sanitaria Territoriale di Cremona, Cremona, Italy dgenerali@units.it. FAU - Montemurro, Filippo AU - Montemurro F AD - Divisione di Oncologia Clinica Investigativa dell'Istituto di Candiolo-IRCCS, Candiolo, Italy. FAU - Bordonaro, Roberto AU - Bordonaro R AD - ARNAS Garibaldi Nesima, Catania, Italy. FAU - Mafodda, Antonino AU - Mafodda A AD - Divisione Oncologia Medica, A.O. Bianchi Melarino Morelli, Reggio Calabria, Italy. FAU - Romito, Sante AU - Romito S AD - Reparto di Oncologia Medica, Ospedali Riuniti di Foggia, Foggia, Italy. FAU - Michelotti, Andrea AU - Michelotti A AD - U.O. Oncologia Medica, Ospedale Santa Chiara, Pisa, Italy. FAU - Piovano, Pierluigi AU - Piovano P AD - Divisione Oncologia Medica, Presidio Santi Antonio e Biagio, Alessandria, Italy. FAU - Ionta, Maria Teresa AU - Ionta MT AD - Clinica Oncologica Medica, Policlinico Monserrato, Monserrato, Italy. FAU - Bighin, Claudia AU - Bighin C AD - Reparto Oncologia Medica A, Istituto Nazionale Ricerca sul Cancro, Genova, Italy. FAU - Sartori, Donata AU - Sartori D AD - Divisione Oncologia Ematologia, Presidio Ospedaliero di Mirano, Venezia, Italy. FAU - Frassoldati, Antonio AU - Frassoldati A AD - Reparto Oncologia Clinica, Ospedale Sant'Anna di Cona, Ferrara, Italy. FAU - Cazzaniga, Marina Elena AU - Cazzaniga ME AD - Oncologia, Azienda Ospedalierra San Gerardo, Monza, Italy. FAU - Riccardi, Ferdinando AU - Riccardi F AD - U.O.C. Oncologia Medica, Ospedale Cardarelli, Napoli, Italy. FAU - Testore, Franco AU - Testore F AD - Day Hospital Oncologia, Ospedale Cardinale Guglielmo Massaia, Asti, Italy. FAU - Vici, Patrizia AU - Vici P AD - Divisione Oncologia Medica B, IRE IRCCS Regina Elena, Roma, Italy. FAU - Barone, Carlo Antonio AU - Barone CA AD - U.O.C Oncologia Medica, Policlinico Universitario A, Gemelli, Roma. FAU - Schirone, Alessio AU - Schirone A AD - Day Hospital Oncoematologia, IRST Istituto Scientifico Romagnolo, Meldola, Italy. FAU - Piacentini, Federico AU - Piacentini F AD - Division of Medical Oncology Department of Medical and Surgical Sciences for Children & Adults University Hospital of Modena, Modena, Italy. FAU - Nole, Franco AU - Nole F AD - Divisione Oncologia Medica Urogenitale, Istituto Europeo di Oncologia, Milano, Italy. FAU - Molino, Annamaria AU - Molino A AD - Oncologia, Universita di Verona, Italy. FAU - Latini, Luciano AU - Latini L AD - Day Hospital Oncologia, Ospedale di Macerata, Macerata, Italy. FAU - Simoncini, Edda Lucia AU - Simoncini EL AD - Breast Unit Spedali Civili di Brescia, Brescia, Italy. FAU - Roila, Fausto AU - Roila F AD - Divisione Oncologia Medica, Ospedale Civile Santa Maria, Terni. FAU - Cognetti, Francesco AU - Cognetti F AD - Divisione Oncologia Medica A, IRE IRCCS Regina Elena, Roma, Italy. FAU - Nuzzo, Francesco AU - Nuzzo F AD - U.O.C. Oncologia Medica Senologica, Istituto Nazionale Tumori Fondazione Pascale, Napoli, Italy. FAU - Foglietta, Jennifer AU - Foglietta J AD - U.O. Oncologia Medica, Ospedale Santa Maria della Misericordia, Perugia, Italy. FAU - Minisini, Alessandro Marco AU - Minisini AM AD - Dipartimento di Oncologia, Azienda Sanitaria Universitaria Integrata, Udine, Italy. FAU - Goffredo, Francesca AU - Goffredo F AD - Novartis Farma S.p.A, Origgio, Italy. FAU - Portera, Giuseppe AU - Portera G AD - Novartis Farma S.p.A, Origgio, Italy. FAU - Ascione, Gilda AU - Ascione G AD - Novartis Farma S.p.A, Origgio, Italy. FAU - Mariani, Gabriella AU - Mariani G AD - Divisione Oncologia Medica 1, IRCCS Istituto Nazionale dei Tumori, Milano, Italy. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20170421 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Androstadienes) RN - 9HW64Q8G6G (Everolimus) RN - NY22HMQ4BX (exemestane) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Androstadienes/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Breast Neoplasms/*drug therapy/pathology MH - Drug-Related Side Effects and Adverse Reactions/classification/pathology MH - Everolimus/*administration & dosage/adverse effects MH - Female MH - Humans MH - Italy MH - Middle Aged MH - Neoplasm Metastasis PMC - PMC5469582 OTO - NOTNLM OT - Advanced breast cancer OT - Everolimus OT - Hormone-receptor positive OT - Real life OT - Safety COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2017/04/23 06:00 MHDA- 2018/03/17 06:00 PMCR- 2018/06/01 CRDT- 2017/04/23 06:00 PHST- 2016/11/23 00:00 [received] PHST- 2017/01/10 00:00 [accepted] PHST- 2017/04/23 06:00 [pubmed] PHST- 2018/03/17 06:00 [medline] PHST- 2017/04/23 06:00 [entrez] PHST- 2018/06/01 00:00 [pmc-release] AID - theoncologist.2016-0461 [pii] AID - ONCO12114 [pii] AID - 10.1634/theoncologist.2016-0461 [doi] PST - ppublish SO - Oncologist. 2017 Jun;22(6):648-654. doi: 10.1634/theoncologist.2016-0461. Epub 2017 Apr 21.