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Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population

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Abstract

Background

The addition of everolimus to exemestane therapy significantly improves progression-free survival in postmenopausal patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant breast cancer. However, the safety profile of this schedule still might be optimized.

Methods

Patients included in the BALLET trial were assessed. The objectives of this analysis were to provide additional information on the safety profile of this schedule depending on prior anticancer therapies and to characterize the time course of adverse events (AEs) and serious AEs (SAEs) of clinical interest throughout the study period. Non-infectious pneumonitis (NIP), stomatitis, asthenia and weight loss were selected as AEs of clinical interest.

Results

The safety population of this analysis comprised 2131 patients. There were similar incidences of AEs and SAEs of clinical interest regardless of previous anticancer therapies. Most stomatitis and asthenia events occurred within the first three months. Incidence of weight loss appeared to plateau except in the case of grade 3–4 events, which occurred rarely. The incidence of any grade NIP (between 2 to 6%) and grade 3–4 NIP (between 0 to 1%) was low across the study, but steady.

Conclusions

Everolimus plus exemestane is a well-known therapeutic option for aromatase inhibitor pretreated advanced breast cancer patients, and its toxicity profile is similar to that described in previous studies. Close monitoring, especially within the first three months, early intervention with preventive measures and patient education to help recognize the first signs and symptoms of AEs, will help to reduce their incidence and severity.

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Acknowledgements

The authors wish to thank Beatriz Gil-Alberdi from HealthCo SL (Madrid, Spain) for her help in the preparation of the first draft of this manuscript.

Funding

Novartis Spain provided financial support for medical writing services.

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Authors and Affiliations

  1. Department of Medical Oncology, Breast Cancer Unit, University Hospital 12 de Octubre, Avda. De Córdoba, s/n, 28041, Madrid, Spain

    E. Ciruelos

  2. Centre Hospitalier Universitaire du Sart-Tilman, University of Liege, Liège, Belgium

    G. Jerusalem

  3. Department of Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, GEICAM, CIBERONC, Madrid, Spain

    M. Martin

  4. Department of Medical Oncology, GROW, Maastricht University Medical Centre, Maastricht, The Netherlands

    V. C. G. Tjan-Heijnen

  5. Department of Oncology, Multidisciplinary Breast Center, KULeuven-University of Leuven, Leuven, Belgium

    P. Neven

  6. Department of Medical Oncology, Instituto Valenciano de Oncologia, Valencia, Spain

    J. Gavila

  7. Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy

    F. Montemurro

  8. Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy

    D. Generali

  9. Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary

    I. Lang

  10. Medical Department, Novartis Oncology, Barcelona, Spain

    M. J. Martínez-Serrano & M. F. Perelló

  11. Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy

    P. Conte

  12. Medical Oncology, Istituto Oncologico Veneto, Padova, Italy

    P. Conte

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by EC, MFP and MJM-S. All authors commented on previous versions and approved the final manuscript.

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Correspondence to E. Ciruelos.

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Conflict of interest

E. Ciruelos declare her participation in advisory boards of Roche, Lilly, Pfizer and Novartis and received speakers’ honoraria from Roche, Lilly, Pfizer and Novartis as well as non-financial support from Roche. G. Jerusalem declare research grants from Novartis, Roche and Pfizer, personal fees from Novartis, Roche, Pfizer, Lilly, Celgene, Amgen, BMS and AstraZeneca, and non-financial support from Novartis, Roche, Lilly, Pfizer, Amgen, BMS and AstraZeneca. M. Martin declare research grants from Roche and Novartis, speaker’s honoraria from Roche, AstraZeneca, GSK, Pfizer and Lilly and participated in advisory boards of Roche, AstraZeneca, GSK, Lilly, Pfizer Taiho and Pharmamar. V. C. G. Tjan-Heijnen declare research grants and non-financial support from Novartis, Pfizer, Roche, Lilly and AstraZeneca. J. Gavila declare speakers’ honoraria and participation in advisory boards from Pfizer, Roche and Novartis. F. Montemurro declare speakers’ honoraria from Novartis, Lilly and Pfizer and participated in advisory boards of Roche. D. Generali declare speakers’ honoraria from Novartis, Lilly and Pfizer. M. J. Martínez-Serrano and M. F. Perelló are Novartis’ employees. P. Neven and I. Lang and P. Conte declare that they have no conflict of interest.

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This study has been performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments and comply with the current laws of the countries in which they were performed.

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Ciruelos, E., Jerusalem, G., Martin, M. et al. Everolimus plus exemestane in hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: incidence and time course of adverse events in the phase IIIb BALLET population. Clin Transl Oncol 22, 1857–1866 (2020). https://doi.org/10.1007/s12094-020-02327-5

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