Thursday, August 9, 2012 (Last Updated: 08/10/2012)
Gustavo Ismael, M.D., from the Hospital Amaral Carvalho in Jaú, Brazil, and colleagues conducted a phase 3, randomized, open-label trial to compare the pharmacokinetic profile, efficacy, and safety of the subcutaneous and intravenous formulations of trastuzumab in the treatment of HER2-positive early breast cancer. Participants with HER2-positive, operable, locally advanced or inflammatory breast cancer were randomized to neoadjuvant chemotherapy administered concurrently with either intravenous trastuzumab (299 patients; 8 mg/kg loading dose and 6 mg/kg maintenance dose given every three weeks) or subcutaneous trastuzumab (297 patients; fixed dose of 600 mg given every three weeks). Patients continued with trastuzumab after surgery to complete one year of treatment.
The researchers found that, in the intravenous and subcutaneous groups, the geometric mean presurgery serum trough concentration (Ctrough) was 51.8 and 69.0 µg/mL, respectively, for a ratio of Ctrough subcutaneous to Ctrough intravenous of 1.33. A pathologic complete response was achieved by 40.7 and 45.4 percent in the intravenous and subcutaneous groups, respectively. Subcutaneous trastuzumab was considered non-inferior to intravenous trastuzumab. The incidence of grade 3 to 5 adverse events was comparable between the groups, with more patients in the subcutaneous group experiencing serious adverse events than in the intravenous group (21 versus 12 percent). There were two treatment-related deaths in the subcutaneous group.
"Subcutaneous trastuzumab, administered over about five minutes, has a pharmacokinetic profile and efficacy non-inferior to standard intravenous administration, with a similar safety profile to intravenous trastuzumab, and therefore offers a valid treatment alternative," the authors write.
Several authors disclosed financial ties to F. Hoffmann-La Roche, which funded the study and manufactures trastuzumab.
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