Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer
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Published:2023-10-01
Issue:10
Volume:9
Page:1381
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ISSN:2374-2437
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Container-title:JAMA Oncology
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language:en
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Short-container-title:JAMA Oncol
Author:
Huober Jens12, Weder Patrik12, Ribi Karin3, Thürlimann Beat1, Thery Jean-Christophe4, Li Qiyu2, Vanlemmens Laurence5, Guiu Séverine6, Brain Etienne7, Grenier Julien8, Dalenc Florence9, Levy Christelle10, Savoye Aude-Marie11, Müller Andreas12, Membrez-Antonioli Véronique13, Gérard Marie-Aline2, Lemonnier Jérôme14, Hawle Hanne2, Dietrich Daniel2, Boven Epie15, Bonnefoi Hervé16, Popescu Razvan17, Schreiber Alexander17, Caspar Clemens17, Cescato- Wenger Corinne17, Rochlitz Christoph17, Condorelli Rosaria17, Rabaglio-Poretti Manuela17, Borner Markus17, Mengis Bay Catherine17, Jost Lorenz M.17, von Moos Roger17, Fehr Mathias17, Bodmer Alexandre17, Zaman Khallil17, Seifer Bettina17, Calderoni Antonello17, Aebi Stefan Paul17, Uhlmann Nussbaum Catrina17, Riniker Salome17, Bolliger Barbara17, Ackermann Christoph17, Dedes Konstantin17, Bihan Céline17, Capitain Olivier17, Arsene Olivier17, Simon Hélène17, Rastkhah Mansour17, Coudert Bruno17, Mousseau Mireille17, Venat- Bouvet Laurance17, Lamy Régine17, Brunel Véronique17, Goncalves Anthony17, Largillier Rémy17, Spaeth Dominique17, Vannetzel Jean- Michel17, Ferrero Jean- Marc17, Ricci Francesco17, Rosca Cristina17, Baron Marc17, Campone Mario17, Jacquin Jean- Philippe17, Serra Sebastian17, Del Piano Francesco17, Dramais Marcel Dominique17, Ovign Irma17, Smorenburg Carolien17, Konings Inge17, Houtsma Daniel17, Kessels Lonneke17, van Warmerdam Laurance17, de Graaf Hiltje17, Kroep Judith17, Agterof Mariette17, van Rossum- Schornagel Quirine17, Van Leeuwen Elise17, Benavent Valérie17, Pilop Christiane17, Lemonier Jerôme17, Martin Anne Laure17, Ölschlegel Christiane17, Gérard Marie- Aline17, Gnant Michael17, Loibl Sybille17, Tondini Carlo17,
Affiliation:
1. Breast Center St Gallen, Cantonal Hospital St Gallen, St Gallen, Switzerland 2. Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland 3. Quality of Life Office, International Breast Cancer Study Group, Bern, Switzerland 4. Department of Medical Oncology, Center Henri Becquerel, Rouen, France 5. Department of Medical Oncology, Center Oscar Lambret, Lille, France 6. Department of Medical Oncology, Regional Cancer Institute, Montpellier, France 7. Department of Medical Oncology, Institute Curie, Paris & Saint-Cloud, France 8. Department of Medical Oncology, Institute Sainte Catherine, Avignon, France 9. Department of Medical Oncology, Institute Claudius Regaud–Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France 10. Department of Medical Oncology, Center Francois Baclesse, Caen, France 11. Department of Medical Oncology, Institute Jean Godinot, Reims, France 12. Breast Center, Cantonal Hospital of Winterthur, Winterthur, Switzerland 13. Department of Medical Oncology, Hospital of Valais, Sion, Switzerland 14. R&D, Unicancer, Paris, France 15. Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam/Cancer Center Amsterdam, Amsterdam, the Netherlands 16. Department of Medical Oncology, Institut Bergonié Unicancer, Universitaire Bordeaux, Institut National de la Santé et de la Recherche Médicale U1218, Bordeaux, France 17. for the Swiss Group for Clinical Cancer Research, Unicancer Breast Group, and Dutch Breast Cancer Research Group
Abstract
ImportanceIn ERBB2 (formerly HER2)-positive metastatic breast cancer (MBC), combining trastuzumab and pertuzumab with taxane-based chemotherapy is the first line of standard care. Given that trastuzumab plus pertuzumab was proven effective in ERBB2-positive MBC, even without chemotherapy, whether the optimal first-line strategy could be trastuzumab plus pertuzumab alone instead of with chemotherapy is unresolved.ObjectiveTo assess overall survival (OS) at 2 years and progression-free survival (PFS) for patients randomly assigned to receive first-line pertuzumab plus trastuzumab alone or with chemotherapy followed by trastuzumab and emtansine at progression; PFS of second-line trastuzumab and emtansine treatment following trastuzumab plus pertuzumab; and OS and PFS in the ERBB2-enriched and ERBB2-nonenriched subtypes.Design, Setting, and ParticipantsThis was a secondary analysis of a multicenter, open-label, phase 2 randomized clinical trial conducted at 27 sites in France, 20 sites in Switzerland, 9 sites in the Netherlands, and 1 site in Germany. Overall, 210 patients with centrally confirmed ERBB2-positive MBC were randomized between May 3, 2013, and January 4, 2016, with termination of the trial May 26, 2020. Data were analyzed from December 18, 2020, to May 10, 2022.InterventionsPatients randomly received pertuzumab (840 mg intravenously [IV], then 420 mg IV every 3 weeks) plus trastuzumab (8 mg/kg IV, then 6 mg/kg IV every 3 weeks) without chemotherapy (group A) or pertuzumab plus trastuzumab (same doses) with either paclitaxel (90 mg/m2 for days 1, 8, and 15, then every 4 weeks for ≥4 months) or vinorelbine tartrate (25 mg/m2 for first administration followed by 30 mg/m2 on days 1 and 8 and every 3 weeks for ≥4 months) followed by pertuzumab plus trastuzumab maintenance after chemotherapy discontinuation (group B).Main Outcomes and MeasuresOverall survival at 24 months by treatment group, PFS for first-line treatment, PFS for second-line treatment, and patient-reported quality of life (QOL).ResultsA total of 210 patients were included in the analysis, with a median age of 58 (range, 26-85) years. For group A, 24-month OS was 79.0% (90% CI, 71.4%-85.4%); for group B, 78.1% (90% CI, 70.4%-84.5%). Median PFS with first-line treatment was 8.4 (95% CI, 7.9-12.0) months in group A and 23.3 (95% CI, 18.9-33.1) months in group B. Unlike expectations, OS and PFS did not markedly differ between populations with ERBB2-enriched and ERBB2-nonenriched cancer. Adverse events were less common without chemotherapy, with small QOL improvements from baseline in group A and stable QOL in group B.Conclusions and RelevanceThe findings of this secondary analysis of a randomized clinical trial suggest that the chemotherapy-free anti-ERBB2 strategy is feasible without being detrimental in terms of OS. The 50-gene prediction analysis of microarray signature could not help to identify the most appropriate patient population for this approach.Trial RegistrationClinicalTrials.gov Identifier: NCT01835236
Publisher
American Medical Association (AMA)
Subject
Oncology,Cancer Research
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