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. 2014 Apr;74(4):343-349.
doi: 10.1055/s-0034-1368173.

Subcutaneous Administration of Monoclonal Antibodies in Oncology

C Jackisch  1 , V Müller  2 , C Maintz  3 , S Hell  4 , B Ataseven  5
Affiliations

Subcutaneous Administration of Monoclonal Antibodies in Oncology

C Jackisch et al. Geburtshilfe Frauenheilkd. 2014 Apr.

Abstract
in English, German

Treatment with monoclonal antibodies (mabs) has become an established component of oncological therapy. The monoclonal antibodies available for this purpose are mainly administered intravenously in individually adapted doses according to body weight over longer treatment times. For other chronic diseases such as, for example, diabetes mellitus, the subcutaneous administration of drugs is an established therapy option. For the subcutaneous administration of larger volumes as needed for mab solutions the extracellular matrix of the subcutaneous tissue represents a problem. The co-formulation with recombinant human hyaluronidase makes the relatively pain-free administration of larger fluid volumes and thus the subcutaneous administration of monoclonal antibodies possible, as illustrated by the development of a subcutaneous formulation of trastuzumab. This constitutes a less invasive, time-optimised and flexible form of administration for patients with HER2-positive breast cancer that, with its fixed dosing possibilities, contributes to therapeutic safety. The example of trastuzumab shows that the subcutaneous administration of monoclonal antibodies can simplify oncological long-term therapy not only for the patients but also for the medical personnel.

Die Behandlung mit monoklonalen Antikörpern (mAK) ist ein fester Bestandteil der onkologischen Therapie geworden. Die dafür zur Verfügung stehenden monoklonalen Antikörper werden überwiegend intravenös, individualisiert gewichtsadaptiert und über längere Behandlungszeiträume verabreicht. Bei anderen chronischen Erkrankungen wie beispielsweise Diabetes mellitus stellt die subkutane Applikation von Medikamenten, eine etablierte Therapieform dar. Für die subkutane Applikation größerer Volumina stellt die Physiologie der extrazellulären Matrix des subkutanen Gewebes ein Hindernis dar, wie sie für die Lösung mAK erforderlich ist. Die Koformulierung mit rekombinanter humaner Hyaluronidase ermöglicht die schmerzarme Gabe größerer Volumina und damit die subkutane Applikation von monoklonalen Antikörpern, wie die Entwicklung einer subkutanen Formulierung für Trastuzumab zeigt. Mit dieser steht Patientinnen mit HER2-positivem Mammakarzinom eine weniger invasive, zeitoptimierte und flexiblere Applikationsform zur Verfügung, die mit einer fixen Dosierungsmöglichkeit zur Therapiesicherheit beiträgt. Das Beispiel Trastuzumab zeigt, dass die subkutane Verabreichung monoklonaler Antikörper die onkologische Langzeittherapie sowohl für Patienten als auch für medizinisches Fachpersonal vereinfachen könnte.

Keywords: breast cancer; monoclonal antibodies; oncology; subcutaneous therapy; trastuzumab.

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Conflict of interest statement

Conflict of Interest The authors declare that within the past 3 years they have been active or received support as follows: CJ consultancy fees from Roche, travel expenses from Roche and Amgen; VM fees for consultations and expertise from Roche, lectures for Roche, Colene, Pierre Fabre, travel expenses from GBG Forschungs GmbH; CM fees for the performance of contracted clinical studies from Roche; SH consultancy fees from Roche; BA fees for consultations, lectures and contracted clinical studies from Roche, travel expenses from Roche.

Figures

Fig. 1 a
Fig. 1 a
and b Principle of subcutaneous administration using recombinant human hyaluronidase as carrier. a The subcutaneous tissue with its matrix of hyaluronic acid and collagen fibres limits the subcutaneous administration to volumes < 2 mL. b The temporary and local degradation of hyaluronic acid by recombinant human hyaluronidase leads to a temporary increase in the subcutaneous dispersion surface and makes possible the administration of larger fluid volumes (source: Hoffmann-La Roche).
Fig. 2
Fig. 2
Trastuzumab exposure in patients with HER2-positive early breast cancer for the doses 8 mg/kg s. c. and 6 mg/kg i. v. (after Wynne et al. 27). * The Ctrough of 20 µg/mL reflects the target value established in preclinical xenograft models.
Fig. 3
Fig. 3
Results for the co-primary endpoints for trastuzumab s. c. vs. i. v. in the HannaH trial (after Ismael et al. 30).
See this image and copyright information in PMC

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