Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.

Autor:	de Azambuja E; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium. Electronic address: evandro.azambuja@bordet.be., Agostinetto E; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium., Procter M; Frontier Science, Kincraig, Kingussie, UK., Eiger D; F.Hoffmann-La Roche Ltd, Basel, Switzerland., Pondé N; Clinical Oncology Department, AC Camargo Cancer Center, São Paulo, Brazil., Guillaume S; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium., Parlier D; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium., Lambertini M; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Sciences (DiMI), School of Medicine, University of Genova, Genova, Italy., Desmet A; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium., Caballero C; Breast International Group, Brussels, Belgium., Aguila C; F.Hoffmann-La Roche Ltd, Basel, Switzerland., Jerusalem G; CHU Liege and Liege University, Liege, Belgium., Walshe JM; Cancer Trials Ireland, St Vincent's University Hospital, Dublin, Ireland., Frank E; Dana-Farber Cancer Institute, Boston, USA., Bines J; Instituto Nacional de Cancer, INCA, Rio de Janeiro, Brazil., Loibl S; German Breast Group, Neu-Isenburg, Germany., Piccart-Gebhart M; Institut Jules Bordet and L'Université Libre de Bruxelles (U.L.B), Brussels, Belgium., Ewer MS; University of Texas, MD Anderson Cancer Center, Houston., Dent S; Duke Cancer Institute, Duke University, Durham, USA., Plummer C; Department of Cardiology, Freeman Hospital, Newcastle upon Tyne, UK., Suter T; Department of Cardiology, Cardio-Oncology, Bern University Hospital, Bern, Switzerland.
Jazyk:	angličtina
Zdroj:	ESMO open [ESMO Open] 2023 Feb; Vol. 8 (1), pp. 100772. Date of Electronic Publication: 2023 Jan 19.
DOI:	10.1016/j.esmoop.2022.100772
Abstrakt:	Background: Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. Patients and Methods: Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. Results: The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m 2 , baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). Conclusions: Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors. Competing Interests: Disclosure EdA: Honoraria and/or advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac, Libbs, and Pierre Fabre. Travel grants from Roche/GNE, and GSK/Novartis. Research grant to his institution from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier. EA: Consultancy fees/honoraria: Eli Lilly, Sandoz, and AstraZeneca. Support for attending medical conferences from: Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, and Daiichi Sankyo (all outside the submitted work). MP: Her institution received funding from Roche in respect to the APHINITY trial. DE: Employment: Roche. Stock and Other Ownership Interests: Roche; Research Funding: Novartis. NP is an employee of IQVIA Biotech. ML: Honoraria and/or advisory board from Roche, Novartis, Lilly, Pfizer, AstraZeneca, Gilead, Seagen, MSD, Exact Sciences, Takeda, Ipsen, Sandoz, Libbs, and Knight. CC: Her institution received research funding from: AstraZeneca, Roche/Genentech, Tesaro, Novartis, Pfizer, SERVIER, Biovica, GlaxoSmithKline, and Sanofi/Aventis. Her institution receives royalties from Agendia for MammaPrint. CA: Full-time employment, Medical Director for F. Hoffmann-La Roche Ltd, and own stock in F. Hoffmann-La Roche Ltd. GJ: Honoraria and/or advisory board Novartis, Roche, Amgen, Pfizer, Bristol-Myers Squibb, Lilly AstraZeneca, Seagen, Daiichi Sankyo, and Abbvie. Research grant to the institution Novartis, Roche, and Pfizer. JMW: Honoraria and/or advisory board from Roche/GNE, Novartis, and AstraZeneca. JB: Honoraria and/or advisory board from AstraZeneca, Daiichi Sankyo, Eli Lilly, Genomic Health, Libbs, MSD, Novartis, Pfizer, and Roche. SL: Grants, non-financial support and other from Roche, during the conduct of the study; grants and other from Abbvie, other from Amgen, grants and other from AstraZeneca, other from Bayer, other from BMS, grants and other from Celgene, other from Eirgenix, other from GSK, grants, non-financial support and other from Immunomedics/Gilead, other from Lilly, other from Merck, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, other from Prime/Medscape, non-financial support and other from Puma, other from Samsung, non-financial support and other from Seagen, grants, non-financial support and other from Daiichi Sankyo, outside the submitted work; In addition, SL has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending, and a patent Digital Ki67 Evaluator with royalties paid. MP-G: Consultant honoraria: Oncolytics (Scientific Board), AstraZeneca, Camel-IDS/Precirix, Gilead, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Pfizer, Roche-Genentech, Seattle Genetics, Immutep, Seagen, NBE Therapeutics, Frame Therapeutics; Research grants to my Institute: AstraZeneca, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, and Synthon. MSE: Consultant for Boehringer Ingelheim and Beyer. Receives book royalties for Cancer and the Heart.SD: Honoraria/advisory boards from Novartis and AstraZeneca; research grant Novartis. CP: Honoraria and/or advisory board from Amgen, Celgene, Incyte, Ipsen, and Novartis. All other authors have declared no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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