Clinical benefit of trastuzumab (H) among patients with HER2-positive metastatic breast cancer (MBC) not achieving objective responses when treated with H plus chemotherapy (CT)

680 Background: Clinical benefit from cytotoxic CT is observed largely in those patients with objective clinical response (OCR). This may not be the case, however, for targeted biologic agents with cytostatic mechanisms of action. H elicits cell cycle arrest in HER2-amplified cells via perturbation of HER2 signal transduction. Such mechanisms of action of H may not result in OCR, but rather induce disease stabilization. Methods: To test this hypothesis, we performed a retrospective analysis of the subset of patients not achieving an OCR from the pivotal phase III clinical trial of CT (either anthracycline/cyclophosphamide [AC] or paclitaxel [T]) with or without H in women with MBC (Slamon DJ et al. N Engl J Med 344: 783–792, 2001). A total of 469 patients with HER2 overexpression (2+/3+) by immunohistochemistry (IHC) were enrolled. This analysis focused on time to progression (TTP) and overall survival (OS) for the patients who did not achieve an OCR in the cohort as well as the fluorescence in situ hybri...