Impact of HER2-targeted therapy on overall survival (OS) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC).

Abstract

572 Background: Trastuzumab (T) prolongs OS over chemotherapy alone in pts with HER2+ MBC. Upon disease progression, pts may switch to lapatinib (L) or continue on T. We aimed at assessing the impact of both strategies on OS in all pts treated for HER2+ MBC at the Department of Medicine 1, Medical University of Vienna, from 1999-2009. Methods: 201 pts were identified from a BC databank. 115 pts (572%) received multiple lines of T, whereas 58 (28.9%) were treated with a single line of T-based palliative therapy. A control group of 28 pts (13.9%) had never received T as they were treated before 1999, when T was introduced. HER2 was determined by immunohistochemistry and reanalyzed by FISH if a score of 2+ was gained. OS from diagnosis of metastatic disease was defined as primary study endpoint and estimated using the Kaplan-Meier method. A Cox proportional hazards model was applied to correct for other factors associated with OS. Results: T significantly prolonged OS in HER2+ MBC (41 vs. 13 months; p<0.001). T in multiple lines further numerically improved OS (47 vs. 28 months; p=0.069), which however did not reach statistical significance. In the Cox regression model, brain metastases (BM) (HR 0.67; 95% CI 0.47-0.96) predicted for shorter OS, while positive estrogen receptor (ER) status (HR 1.6; 95% CI 1.13-2.27) was significantly associated with better outcome. Addition of L did not further improve OS in patients receiving multiple lines of T (62 vs. 47 months; p=n.s.), while in pts with BM, L improved OS in an univariate model (6 pts; 22 vs. 5 months; p=0.022). Furthermore, numerically less pts treated with L developed BM (30.8% vs. 39.6%; p=n.s.). Incidence of BM in the total sample was 39% and was independent of ER-status (44% vs. 37%; p=n.s.). Conclusions: Introduction of T improved OS in pts with HER2+ MBC, with a further numerical improvement when administered in multiple lines. As in HER2-negative tumours, ER-negative disease was associated with worse outcome, although no higher risk for BM was observed. In this homogenous sample of pts treated with T in multiple lines, L did not further improve OS; however, L might reduce the risk for developing BM and improve OS in pts with BM.