Subcutaneous administration of trastuzumab (Herceptin) appears to be as safe and effective as the much more time-consuming intravenous (IV) delivery system.
Patients with HER2-positive, clinical stage I–III breast cancer who receive trastuzumab, a monoclonal antibody that targets the HER2 protein, currently have to take the drug intravenously. This entails being connected to a drip for 90 minutes for the initial dose, and then for 30 minutes, usually once every 3 weeks, for subsequent doses. However, a new subcutaneous formulation of trastuzumab that takes approximately 5 minutes to administer appears to offer a valid treatment alternative.
In the randomized study designed to test injectable trastuzumab, 299 women with HER2-positive, operable, locally advanced, or inflammatory breast cancer were assigned to receive eight cycles of neoadjuvant chemotherapy administered concurrently with trastuzumab every 3 weeks intravenously (8 mg/kg loading dose, 6 mg/kg maintenance dose). Another 297 women received the same chemotherapy plus subcutaneous trastuzumab (fixed dose of 600 mg).
Pathological complete response was achieved in 40.7% of IV patients and 45.4% of subcutaneous users. The occurrence of grade 3 to 5 adverse events was similar between groups. The most common such event, neutropenia, was experienced by 33.2% of the IV group and 29% of the subcutaneous group, followed by leucopenia (5.7% and 4%, respectively) and febrile neutropenia (3.4% vs 5.7%, respectively).
However, a greater number of serious adverse events occurred in the subcutaneous group (62 of 297 patients [21%], compared with 37 of 298 patients [12%]), mainly due to infections and infestations in 8.1% of the subcutaneous group compared with 4.4% of the IV group. Of the three adverse events in the subcutaneous group that led to death (compared with one in the IV group), two were deemed to be treatment-related. All deaths occurred during the neoadjuvant phase.
Despite these incidents, the investigators concluded in The Lancet Oncology (2012;13:869-878) that subcutaneously delivered trastuzumab offers a valid treatment alternative to IV administration.