Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study
Mattea Reinisch,
Michael Untch,
Rolf Mahlberg,
Toralf Reimer,
Thomas Hitschold,
Frederik Marmé,
Mustafa Aydogdu,
Sabine Schmatloch,
Hans-Joachim Lück,
Marcus Schmidt,
Ekkehart Ladda,
Bruno Valentin Sinn,
Peter Klare,
Wolfgang Janni,
Christian Jackisch,
Carsten Denkert,
Sabine Seiler,
Thomas Göhler,
Laura Michel,
Nicole Burchardi,
Elmar Stickeler,
Julia Rey,
Nicole Klutinus,
Volker Möbus,
Sibylle Loibl
Affiliations
Mattea Reinisch
Interdisciplinary Breast Unit, Kliniken Essen-Mitte, Essen, Germany
Michael Untch
Department of Gynaecology and Obstetrics, Breast Cancer and Gynecologic Oncology Center, HELIOS Klinikum Berlin Buch, Germany
Rolf Mahlberg
Klinikum Mutterhaus der Borromäerinnen, Trier, Germany
Toralf Reimer
Universitätsfrauenklinik und Poliklinik Am Klinikum Südstadt Rostock, Germany
Thomas Hitschold
Klinikum Worms, Frauenklinik, Germany
Frederik Marmé
Department of Gynaecology and Obstetrics, University Hospital Mannheim, Germany
Mustafa Aydogdu
Klinikum Bremen-Mitte, Frauenklinik, Germany
Sabine Schmatloch
Elisabeth Krankenhaus Kassel, Brustzentrum, Germany
Hans-Joachim Lück
Gynaecologic Oncology Practice, Hannover, Germany
Marcus Schmidt
Department of Obstetrics and Gynaecology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Ekkehart Ladda
Onkologische Praxis Neumarkt, Germany
Bruno Valentin Sinn
Department of Pathology, Charité-Universitätsmedizin Berlin, Germany
Peter Klare
Praxisklinik Krebsheilkunde für Frauen Berlin, Germany
Wolfgang Janni
Uniklinikum Ulm, Germany
Christian Jackisch
Sana Klinikum Offenbach, Germany
Carsten Denkert
Institute of Pathology Philipps-University Marburg, Germany
Sabine Seiler
German Breast Group, Neu-Isenburg, Germany
Thomas Göhler
Fachärzte für Innere Medizin, Hämatologie und Internistische Onkologie, Onkozentrum Dresden, Germany
Laura Michel
National Center for Tumour Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany
Department of Medicine II, Haematology & Oncology, University of Frankfurt, Germany
Sibylle Loibl
German Breast Group, Neu-Isenburg, Germany; Corresponding author. author. German Breast Group, GBG Forschungs GmbH, Martin-Behaim-Straße 12, 63263, Neu-Isenburg, Germany.
Background: Trastuzumab given intravenously in combination with chemotherapy is standard of care for patients with early HER2-positive breast cancer (BC). Different randomised studies have shown equivalent efficacy of a subcutaneous injection into the thigh compared to the intravenous formulation. Other body regions for injection have not been investigated but might be more convenient for patients. Methods: After surgery, patients were randomised to receive either subcutaneous trastuzumab into the thigh or into the abdominal wall (AW). Patient preferences were evaluated using validated questionnaires (PINT). Primary objectives of this multicentre, non-blinded, randomised substudy of the GAIN-2 study were to investigate pharmacokinetics of the injection into the thigh versus AW and to determine patients' preferences of either administration site versus the previously received intravenous application. Results: 226 patients were randomised and 219 patients (thigh: N = 110; AW: N = 109) formed the modified intent-to-treat (mITT). Overall, 83.5% (out of N = 182 with information about patients’ preference) preferred subcutaneous over previous intravenous application or had no preference. Preference was similar between both administration sites (thigh: 80.6%; AW: 86.5; p = 0.322). Pharmacokinetic analysis included 30 patients. Geometric means of Cmax and AUC0-21d were higher in thigh than in AW group (geometric mean ratio with body weight adjustment: Cmax: 1.291, 90%-CI 1.052–1.584; AUC0-21d: 1.291, 90%-CI 1.026–1.626). Safety profile was in line with previous reports of subcutaneous trastuzumab. Conclusion: Subcutaneous trastuzumab into the thigh showed an approximately 30% higher bioavailability. Injections were well tolerated and preferred over intravenous administration. The subcutaneous injection into the thigh should remain the standard of care.
