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

Creators: Collet, Laetitia; Eberst, Lauriane; Ludovic, Gauthier; Debled, Marc; Hrab, Loana; Mouret-Reynier, Marie-Ange; Desmoulins, Isabelle; Goncalves, Anthony; Campone, Mario; Ferrero, Jean-Marc; Brain, Etienne; Uwer, Lionel; Eymard, Jean-Christophe; Diéras, Véronique; Simon, Gaëtane; Leheurteur, Marianne; Dalenc, Florence; Vanlemmens, Laurence; Darlix, Amélie; Arnedos, Monica; Bachelot, Thomas

Others:: Department of Medical Oncology [Lyon] ; Centre Léon Bérard [Lyon]; Institut de Cancérologie de Strasbourg Europe (ICANS); Institut régional de Cancérologie de Montpellier (ICM); Institut Bergonié [Bordeaux] ; UNICANCER; Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC) ; Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN); Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP) ; UNICANCER; Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL) ; UNICANCER; Institut Paoli-Calmettes (IPC) ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC); Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO) ; UNICANCER; Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UniCA); Institut Curie - Saint Cloud (ICSC); Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL) ; UNICANCER; Institut Jean Godinot [Reims] ; UNICANCER; CRLCC Eugène Marquis (CRLCC) ; UNICANCER; UNICANCER; Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel); Institut Claudius Regaud; Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille) ; Université de Lille-UNICANCER; Institut de Génomique Fonctionnelle (IGF) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM); Institut Gustave Roussy (IGR)

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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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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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