Efficacy of trastuzumab emtansine (T-DM1) and lapatinib after dual HER2 inhibition with trastuzumab and pertuzumab in patient with metastatic breast cancer: Retrospective data from a French multicenter real-life cohort
Fabien Moinard-Butot,
Caroline Saint-Martin,
Carole Pflumio,
Matthieu Carton,
William Jacot,
Paul-Henri Cottu,
Véronique Diéras,
Florence Dalenc,
Anthony Goncalves,
Marc Debled,
Anne Patsouris,
Marie-Ange Mouret-Reynier,
Laurence Vanlemmens,
Marianne Leheurteur,
George Emile,
Jean-Marc Ferrero,
Isabelle Desmoulins,
Lionel Uwer,
Jean-Christophe Eymard,
Bianca Cheaib,
Coralie Courtinard,
Thomas Bachelot,
Michaël Chevrot,
Thierry Petit
Affiliations
Fabien Moinard-Butot
Department of Medical Oncology, Institut de Cancérologie Strasbourg - Europe (ICANS), 17 Rue Albert Calmette, BP 23025, 67033, Strasbourg, France; Corresponding author.
Caroline Saint-Martin
Department of Biostatistics, Institut Curie, 35 Rue Dailly, 92210, Saint-Cloud, France
Carole Pflumio
Department of Medical Oncology, Institut de Cancérologie Strasbourg - Europe (ICANS), 17 Rue Albert Calmette, BP 23025, 67033, Strasbourg, France
Matthieu Carton
Department of Biostatistics, Institut Curie, 35 Rue Dailly, 92210, Saint-Cloud, France
William Jacot
Department of Medical Oncology, Institut du Cancer de Montpellier, 208 Rue des Apothicaires, 34298, Montpellier, France; Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Montpellier, France
Paul-Henri Cottu
Department of Medical Oncology, Institut Curie, 26 Rue d’Ulm, 75005, Paris, France
Véronique Diéras
Department of Medical Oncology, Centre Eugène Marquis, Avenue de la Bataille Flandres-Dunkerque, 35000, Rennes, France
Florence Dalenc
Department of Medical Oncology, Institut Claudius Regaud – IUCT Oncopole, 1 Avenue Irène-Joliot-Curie, 31059 Toulouse, France
Anthony Goncalves
Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte-Marguerite, 13009, Marseille, France
Marc Debled
Department of Medical Oncology, Institut Bergonié, 229 Cours de l’Argonne, 33000, Bordeaux, France
Anne Patsouris
Department of Medical Oncology, Institut de Cancérologie de l’Ouest Nantes & Angers, 15 Rue André Boquel, 49055, Angers, France
Marie-Ange Mouret-Reynier
Department of Medical Oncology, Centre Jean Perrin, 58 Rue Montalembert, 63011, Clermont Ferrand, France
Laurence Vanlemmens
Medical Oncology Department, Centre Oscar Lambret, 3 Rue Frédéric Combemale, 59000, Lille, France
Marianne Leheurteur
Department of Medical Oncology, Centre Henri Becquerel, Rue d'Amiens, 76000, Rouen, France
George Emile
Department of Medical Oncology, Centre François Baclesse, 3 Avenue du Général Harris, 14000, Caen, France
Jean-Marc Ferrero
Department of Medical Oncology, Centre Antoine Lacassagne, 33 Avenue de Valambrose, 06189, Nice, France
Isabelle Desmoulins
Department of Medical Oncology, Institut de Cancérologie de Bourgogne, 21079, Dijon, France
Lionel Uwer
Medical Oncology Department, Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy, 6 Avenue de Bourgogne, 54519, Vandœuvre-lès-Nancy, France
Jean-Christophe Eymard
Department of Medical Oncology, Institut de Cancérologie Jean-Godinot, 1 Rue du Général Koenig, 51100, Reims, France
Bianca Cheaib
Department of Cancer Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94800, Villejuif, France
Coralie Courtinard
Unicancer, Data Office, 101 Rue de Tolbiac, 75654, Paris, France; Université de Bordeaux, Inserm, Bordeaux Population Health Research Center, Epicene Team, UMR 1219, Bordeaux, France
Thomas Bachelot
Department of Medical Oncology, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008, Lyon, France
Michaël Chevrot
Unicancer, Data Office, 101 Rue de Tolbiac, 75654, Paris, France
Thierry Petit
Department of Medical Oncology, Institut de Cancérologie Strasbourg - Europe (ICANS), 17 Rue Albert Calmette, BP 23025, 67033, Strasbourg, France
Purpose: Trastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal evaluation of these strategies. Methods: ESME Data Platform (NCT03275311) included individual data from all patients aged ≥18 years, in whom first-line treatment for metastatic breast cancer (MBC) was initiated between January 1, 2008 and December 31, 2016 in one of the 18 French Comprehensive Cancer Centers. The efficacy of T-DM1 and lapatinib plus capecitabine combination, following double blockade associating trastuzumab and pertuzumab were evaluated in this national real-life database. Eligibility criteria were: female, MBC, HER2+ tumor, first-line taxane-based chemotherapy and dual HER2-blockage by trastuzumab plus pertuzumab. Cohort A received second-line T-DM1, and Cohort B second-line T-DM1 and third or fourth-line lapatinib plus capecitabine. Results: Cohort A comprised 233 patients, and Cohort B 47 patients. Median progression-free survival (PFS) was 7.1 months in Cohort A and 4.6 months in Cohort B. Median overall survival were 36.7 months and 12.9 months, respectively. PFS was significantly dependent on the preceding treatment line's duration. In cohort A, HER2 expression status was a significant predictive factor of PFS. Conclusion: First-line trastuzumab plus pertuzumab do not markedly diminish T-DM1's efficacy in second-line. Similarly, sequential treatment with trastuzumab plus pertuzumab then T-DM1 does not noticeably modify the efficacy of lapatinib plus capecitabine.