267P - Disease-Free Survival According to Pathologic Response and P95-HER2 in the Cher-Lob Neoadjuvant Study of Chemotherapy Plus Trastuzumab, Lapatinib Or Combined Trastuzumab and Lapatinib In HER2+ Operable Breast Cancer

Abstract

ABSTRACT Introduction This is a randomized phase II trial of preoperative sequential taxanes-anthracyclines in combination with trastuzumab, lapatinib, or combined trastuzumab and lapatinib in HER2 positve operable breast cancer. We previously reported that dual HER2 blockade with trastuzumab and lapatinib significantly increased the pathologic complete response (pCR) rate. The aim of the present post-hoc analysis is the evaluation of disease free survival (DFS) according to pCR, p95-HER2 expression, and treatment arm. Methods 121 patients were randomly assigned to weekly paclitaxel followed by FE75C combined with trastuzumab (arm A, n= 36), lapatinib (arm B, n= 39), or trastuzumab and lapatinib (arm C, n= 46). P95-HER2 expression was measured by IHC (bioTheranostics, Inc. San Diego, CA). Patients were classified as having a p95-HER2 positive tumor in case of strong immunostaining in ≥80% of cells. pCR was defined as disappearance of infiltrating disease in breast and axillary nodes. DFS was calculated from the date of surgery to the date of recurrence (local or distant) or death. Results Overall, pCR was observed in 32% of patients. The pCR rates per treatment arm were 25% in arm A, 26.3% in arm B, and 46.7% in arm C (Arm C vs combined Arms A + B: p = 0.018). Thirty-five patients (29%) resulted p95-HER2 positive. At the time of the present analysis, 17 DFS events have been reported. The expression of p95-HER2 was not significantly correlated with the probability of relapse, overall and per treatment arm. The risk of relapse was significantly lower for patients achieving a pCR (hazard ratio 0.09, p = 0.019). The 3-yr DFS rate was 88% in arm C vs 72% in arms A + B. Conclusions The achievement of a pCR in breast and axillary nodes is predictive of outcome in HER2 positive breast cancer patients treated with neoadjuvant therapy. This is consistent with other neoadjuvant studies. p95-HER2 appears to be neither predictive nor prognostic in this patient population. The combination arm resulted in a trend for a better DFS, probably reflecting the higher pCR rate observed. Sponsored by GlaxoSmithKline. Disclosure C. Holford: Employer GlaxoSmithKline. J. Bruey: Employee at bioTheranostics, Inc. P.F. Conte: GlaxoSmithkline: research funds, speaker's bureau, advisor. All other authors have declared no conflicts of interest.