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Clinical outcome of patients with isolated central nervous system progression on first-line pertuzumab and trastuzumab treatment for HER2-positive metastatic breast cancer in a real-life cohort

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Abstract

Background

More than 10% of HER2-positive metastatic breast cancer (mBC) will develop Central Nervous System (CNS) metastases as first and isolated site of relapse on trastuzumab and pertuzumab first-line therapy. However, few clinical data are available to guide the best strategy in this setting.

Methods

Patients experiencing isolated CNS progression on trastuzumab and pertuzumab first-line therapy were retrospectively identified from the French Epidemiological Strategy and Medical Economics (ESME) real-life database between 2008 and 2016.

Results

Among 995 patients treated with first-line trastuzumab and pertuzumab for HER2-positive mBC, 132 patients (13%) experienced isolated CNS progression with a median time of 12 months after mBC diagnosis. Twelves patients did not receive any treatment and were excluded from the analysis. Among the 120 patients considered, 76 (63%) received CNS-directed local therapy, 73 (60%) continued trastuzumab and pertuzumab, whereas 47 (39%) started another systemic treatment.

After a median follow-up of 21 months, there was no difference in progression-free survival for patient who continued trastuzumab–pertuzumab or switched to another systemic treatment. In multivariate analysis, trastuzumab–pertuzumab continuation was associated with longer OS (HR 0,28 IC 95%: 0,14–0,54 p < 0,001). mOS was not reached (95% 37.6-NE) and was 23.2 months (95% CI 15.5–53.6) in patients who continued trastuzumab and pertuzumab therapy and in patients who switched for another systemic therapy, respectively.

Conclusion

In this real-life cohort, trastuzumab–pertuzumab continuation after local treatment for isolated CNS progression did not negatively impact PFS and OS. Prospective trials and assessment of new strategies are warranted in this specific situation.

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Data availability

Data are indeed available on reasonable request.

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Acknowledgements

We thank the 18 French Comprehensive Cancer Centers for providing the data and each ESME local coordinator for managing the project at the local level. Moreover, we thank the ESME Scientific Group and Strategic Committee for their ongoing support. 18 Participating French Comprehensive Cancer Centers (FCCC): ; I. Curie, Paris/ Saint-Cloud, G. Roussy, Villejuif, I. Cancérologie de l’Ouest, Angers/Nantes, C. F. Baclesse, Caen, ICM Montpellier, C. L. Bérard, Lyon, C. G-F Leclerc, Dijon, C. H. Becquerel, Rouen; I. C. Regaud, Toulouse; C. A. Lacassagne, Nice; Institut de Cancérologie de Lorraine, Nancy; C. E. Marquis, Rennes; I. Paoli-Calmettes, Marseille; C. J. Perrin, Clermont Ferrand; I. Bergonié, Bordeaux; C. P. Strauss, Strasbourg; I. J. Godinot, Reims; C. O. Lambret, Lille. ESME central coordinating staff: Program director: Anne-Laure Martin. Data Management team: Coralie Courtinard, Emilie Nguyen, Olivier Payen, Irwin Piot, Dominique Schwob and Olivier Villacroux. Operational team: Nathalie Bouyer, Michaël Chevrot, Patricia D’Agostino, Pascale Danglot, Levent Dinc, Tahar Guesmia, Charlotte Herlin, Elodie Kupfer, Harmonie Oulie, Sandra Pélissier, Frédéric Roy, Gaëtane Simon and Toihiri Said.Software designer Team: Matou Diop, Blaise Fulpin, Fréja Messo, José Paredes and Alexandre Vanni.

Funding

Industrial partners (Roche, Pierre Fabre Laboratories, Pfizer, AstraZeneca, EISAI, MSD, Daiichi Sankyo, Gilead, Seagen) financially support the ESME MBC database. Unicancer manages the ESME database (i.e., data collection, management analysis, interpretation and publication of the data) independently. None of the industrial partner was involved neither in the design and conduct of the study, nor in collection, management, analysis, and interpretation of the data, nor in preparation, review, or approval of the manuscript nor in decision to submit the manuscript for publication.

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Author notes

  1. Monica Arnedos

    Present address: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France

Authors and Affiliations

  1. Department of Medical Oncology Centre Léon Bérard, 28 Avenue Laënnec, 69008, Lyon, France

    Laetitia Collet & Thomas Bachelot

  2. Department of Medical Oncology, Institut de Cancérologie de Strasbourg, Strasbourg, France

    Lauriane Eberst

  3. Department of Statistics, Institut de Cancérologie de Montpellier, Montpellier, France

    Gauthier Ludovic

  4. Department of Medical Oncology, Institut Bergonié, Bordeaux, France

    Marc Debled & Monica Arnedos

  5. Department of Medical Oncology, Centre François Baclesse, Caen, France

    Loana Hrab

  6. Department of Medical Oncology, Centre Jean Perrin, Clermont-Ferrand, France

    Marie-Ange Mouret-Reynier

  7. Department of Medical Oncology, Centre Georges-François Leclerc, Dijon, France

    Isabelle Desmoulins

  8. Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France

    Anthony Goncalves

  9. Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Angers & Nantes, France

    Mario Campone

  10. Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France

    Jean-Marc Ferrero

  11. Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France

    Etienne Brain

  12. Department of Medical Oncology, Institut de Cancérologie de Lorraine, Nancy, France

    Lionel Uwer

  13. Department of Medical Oncology, Institut Jean Godinot, Reims, France

    Jean-Christophe Eymard

  14. Department of Medical Oncology, Centre Eugène Marquis, Rennes, France

    Veronique Dieras

  15. Real Word Data Department, Data Office, Unicancer, Paris, France

    Gaetane Simon

  16. Department of Medical Oncology, Centre Henri Becquerel, Rouen, France

    Marianne Leheurteur

  17. Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France

    Florence Dalenc

  18. Department of Medical Oncology, Centre Oscar Lambret, Lille, France

    Laurence Vanlemmens

  19. Department of Medical Oncology, Institut Régional du Cancer de Montpellier, Institut de Génomique Fonctionnelle, INSERM, CNRS, University of Montpellier, Montpellier, France

    Amelie Darlix

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Correspondence to Thomas Bachelot.

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Conflict of interest

Laetitia Collet, Lauriane Eberst, Ludovic Gauthier, Marc Debled,, Marie-Ange Mouret-Reynier, Isabelle Desmoulins, Anthony Goncalves, Mario Campone, Jean-Marc Ferrero, Etienne Brain, Lionel Uwer, Jean-Christophe Eymard, Veronique Dieras, Gaetane Simon, Marianne LeLeheurteur, Florence Dalenc, Laurence Vanlemmens, Amelie Darlix: no disclosures. Monica Ardenos: Honoraria: Novartis, Astra Zeneca, Pfizer; Honoraria (to the institution): Roche, Astra Zeneca; Travel grant: Daichii, Pfizer; research grant: Eli-Lilly, Astra Zeneca, Consultant; advisory board (to teh institution): Novartis Loana Hrab: Travel grant: Amgen, Novartis, Pfizer, Sandoz, Pierre Fabre, Mundipharma, Roche Thomas Bachelot: Personal fees and non-financial support from Roche, Novartis, AstraZeneca, grants, Pfizer, personal fees from SeattleGenetics, outside the submitted work.

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Collet, L., Eberst, L., Ludovic, G. et al. Clinical outcome of patients with isolated central nervous system progression on first-line pertuzumab and trastuzumab treatment for HER2-positive metastatic breast cancer in a real-life cohort. Breast Cancer 30, 329–341 (2023). https://doi.org/10.1007/s12282-022-01427-0

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