by 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
The Breast: Published: October 05, 2022
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.
