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)

G. Jerusalem*, G. Mariani, E. M. Ciruelos, M. Martin, V. C. G. Tjan-Heijnen, P. Neven, J. G. Gavila, A. Michelotti, F. Montemurro, D. Generali, E. Simoncini, I. Lang, J. Mardiak, B. Naume, M. Camozzi, K. Lorizzo, S. Bianchetti, P. Conte

*Corresponding author for this work

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Background: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient populationsimilartoBOLERO-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),andserious AEs(SAEs).The secondaryobjectivewastoevaluateAEs ofgrade3/4 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 EXErelatedorEVE/EXE-relatedAEs(investigatorassessed);27.2%wereofgrade3/4severity.Themostfrequentlyreportednonhematologic 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 versuslater lines. Theincidence of AEs (includingstomatitis/pneumonitis)was independent of BMIstatus (post hocanalysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deathswereduetodiseaseprogressionand46(2.2%)duetoAEs;4deathsweresuspectedtobeEVE-related.
Conclusions: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXEand includedasizeable elderlysubset.Although the patients weremore heavily pretreated,thesafetyprofile of EVEplusEXEinBALLETwasconsistentwithBOLERO-2.
Original languageEnglish
Pages (from-to)1719-1725
Number of pages7
JournalAnnals of Oncology
Issue number9
Publication statusPublished - Sep 2016


  • advanced breast cancer
  • BMI
  • elderly
  • everolimus
  • hormone-receptor positive
  • stomatitis

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