267P - Disease-free survival according to pathologic response and p95-HER2 in the CHER-LOB neoadjuvant study of chemotherapy plus trastuzumab, lapatinib or...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Breast Cancer, Early Stage
Pathology/Molecular Biology
Presenter Valentina Guarneri
Authors V. Guarneri1, G. Bisagni2, A. Bottini3, K. Cagossi4, A. Frassoldati5, F. Piacentini1, C. Holford6, J. Bruey7, R. D'Amico1, P.F. Conte1
  • 1Dept. Of Hematology/oncology, Modena University Hospital, 41100 - Modena/IT
  • 2Department Of Oncology, Arcispedale S Maria Nuova, Reggio Emilia/IT
  • 3Unità Di Patologia Mammaria - Breast Unit, Istituti Ospitalieri di Cremona, IT-26100 - Cremona/IT
  • 4Medical Oncology, Ospedale Ramazzini, Carpi (MO)/IT
  • 5Dept Of Clinical Oncology, Azienda Ospedaliera di Ferrara St. Anna, IT-44100 - Ferrara/IT
  • 6Research & Development, GlaxoSmithKline, UB11 1BT - Stockley Park, Uxbridge/UK
  • 7Biomarker Research & Development, bioTheranostics, Inc, San Diego/US

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.