Subcutaneous trastuzumab: a review of its use in HER2-positive breast cancer.
Author(s): Sanford M(1).
Affiliation(s): Author information:
(1)Adis, Springer Healthcare, 41 Centorian Drive, Private Bag 65901, Mairangi
Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
Publication date & source: 2014, Target Oncol. , 9(1):85-94
Trastuzumab (Herceptin®) is a humanized IgG1 monoclonal antibody that is an
efficacious treatment for HER2-positive breast and gastric cancers. Subcutaneous
trastuzumab is a new formulation approved in the European Union for use in
patients with early or metastatic breast cancer. In the randomized, open-label,
multinational HannaH (enHANced treatment with NeoAdjuvant Herceptin) study of
neoadjuvant/adjuvant trastuzumab in patients with early HER2-positive breast
cancer, the pharmacokinetics of neoadjuvant subcutaneous trastuzumab were similar
to those after intravenous administration, meeting the noninferiority criterion
for mean predose trough concentrations, as assessed prior to surgery (primary
pharmacokinetic endpoint). Trastuzumab blood concentrations throughout the dosing
interval remained above those considered necessary for anticancer activity. In
this study, the pathologic complete response rates (primary efficacy endpoint)
were 45.4 and 40.7 % in the subcutaneous and intravenous administration groups,
respectively, meeting a study noninferiority criterion. In the randomized,
open-label, crossover, multinational PrefHer study of neoadjuvant/adjuvant or
adjuvant trastuzumab in early HER2-positive breast cancer, subcutaneous
administration of trastuzumab was preferred over intravenous administration by
>85 % of patients, most commonly because it was time saving and induced less pain
and discomfort. In the HannaH study, the tolerability profile of subcutaneous
trastuzumab was similar to that of intravenous trastuzumab, except that the rate
of serious adverse events was 21 % (vs. 12 % with intravenous administration),
partly because of more infections with subcutaneous administration. Whether this
finding is of any clinical significance should emerge from ongoing studies. On
the evidence, subcutaneous trastuzumab is an effective and generally
well-tolerated treatment option that is preferred by patients over intravenous
administration.
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