Clinical benefit of lapatinib-based therapy in patients with HER2-positive breast tumors expressing p95HER2

Abstract

1048 Background: Approximately 25% of HER2 overexpressing breast tumors express a truncated form of the receptor (p95HER2) that lacks the extracellular domain but retains kinase activity. p95HER2-positive tumors are associated with a worse prognosis and resistant to trastuzumab therapy. In preclinical models, lapatinib (L), a tyrosine kinase inhibitor of EGFR and HER2, is active in p95HER2 expressing tumors. The aim of this analysis was to test the hypothesis that benefit from L-based therapy is independent of p95HER2 expression in 2 clinical trials in patients (pts) with HER2-positive tumors treated with either L monotherapy (Study EGF20009 ) or L in combination with capecitabine (Study EGF100151). Methods: Pre-treatment tumor tissue from both trials (N=201) was analyzed for p95HER2 expression by immunofluorescence as previously described (Scaltriti M. et al, JNCI 2007). Expression of p95HER2 was correlated with clinical benefit rate (CBR: complete response [CR] + partial response [PR] + stable disease [SD] ≥ 24 weeks) and progression-free survival (PFS) using logistic regression and Cox-proportional hazard models. Results: 68/105 and an initial 72/96 tissue samples were evaluable for p95HER2 expression from studies EGF20009 and EGF100151, respectively. The Table summarizes the results from the L treated pts. The CBR and PFS in L treated pts were not significantly different between the p95HER2 subgroups. Expanded data for p95HER2 expression in additional EGF100151 tumor samples will be presented. Conclusions: L as a monotherapy or in combination with capecitabine has similar response activity in pts with p95HER2-positive and p95HER2-negative HER2-positive breast tumors. [Table: see text] [Table: see text]