Subcutaneous trastuzumab: a review of its use in HER2-positive breast cancer

Abstract

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.

Efficacy prediction of targeted therapy for gastric cancer: The current status (Review)

“…HER2-targeted therapy has served an important role in GC drug treatments for a number of years (27)(28)(29), however, there are challenges associated with both intrinsic and acquired drug resistance. In 2014, Eto et al (24) analyzed the over-expression and suppression of the microRNA-21 (miR-21)/phosphatase and tensin homolog (PTEN) pathway in GC cell lines revealing that over-expression of miR-21 led to decreased sensitivity of GC cells to trastuzumab, while the suppression of miR-21 restored the trastuzumab-resistance in GC cell lines.…”

Cost-minimization analysis of subcutaneous versus intravenous trastuzumab administration in Chilean patients with HER2-positive early breast cancer

“…Worldwide, breast cancer (BC) is one of the most prevalent malignancies among women. More than one million new BC cases are diagnosed every year, affecting 43.3/100,000 women and causing >500,000 deaths with a mortality rate of 12.9/100,000 women [1]. In Chilean women, BC is the leading cause of cancer death.…”

“…The mechanism of TZM action involves inhibition of the HER2 intracellular domain, which interferes with cancer cell growth by preventing the activation of cell-proliferation or apoptosis signals [5,6]. The use of TZM in combination with chemotherapy (CT) in the treatment of early-stage HER2+ BC improves survival by up to 35% (with 1 year of TZM use) and reduces the risk of recurrence by 33-52%, including locoregional recurrence [1,4,5,7,8]. Hence, TZM is the current standard treatment for early and advanced HER2+ BC [9].…”

“…That scheme requires healthcare professionals to spend a substantial amount of time on drug preparation and administration procedures. IV-TZM treatment is also a time-consuming procedure from the patients' perspective [1]. The United States food and drug administration (FDA) approved the use of subcutaneous TZM (SC-TZM) in 2013.…”

“…The United States food and drug administration (FDA) approved the use of subcutaneous TZM (SC-TZM) in 2013. The subcutaneous formulation is administered in a single fixed dose of 600 mg over a relatively short time and does not require a loading dose or dose adjustments according to the patient's body weight, meaning a much simpler preparation and more stable doses during the course of treatment, which still involves 18 doses administered over 1 year [1,6]. Thus, compared with IV-TZM, SC-TZM is associated with better optimization of time and financial resources for both patients and medical staff [4,5].…”