P4-08-01: Predictive Value of HER2 Serum Levels in Patients Treated with Lapatinib or Trastuzumab – A Translational Project in the Neoadjuvant “Geparquinto” Trial.

Abstract

Abstract Background Neoadjuvant chemotherapy (NT) has become an important approach to assess therapeutic efficacy of new treatment strategies. We observed a predictive role of of serum HER2 (sHER2) with neoadjuvant trastuzumab treatment in the previous trial “Geparquattro”. Predictive markers for response to new HER2−targeted therapies are still lacking. Therefore, we investigated the role of sHER2 in the context of trastuzumab and lapatinib treatment. Methods: The clinical trial Geparquinto incorporated either trastuzumab or lapatinib treatment combined with chemotherapy for HER2−positive breast cancer patients. Serum samples were taken at three different time points: before initiation of NT, after 4 cycles of chemotherapy with epirubicin and cyclophophamide and after finalization of NT with 4 cycles of docetaxel (pre-surgery). Only those patients were included in the analysis with serum available at all three time points. sHER2 levels were measured by a commercially available ELISA in 159 patients with a HER2−positive primary tumor, 77 (48%) patients were treated with trastuzumab, 82 (52%) with lapatinib. Pathological complete remission (pCR) was defined as no microscopic evidence of invasive residual tumor cells in the breast and lymph nodes. Results: Overall pCR rate in this cohort was 28%. sHER2 levels were higher in patients with larger tumors (> 5cm, p=0.012) and positive nodal status (p=0.001). Higher pre-chemotherapy sHER2 levels were associated with higher pCR rates in the entire study cohort (OR 2.9, 95% CI 1.3−6.7, p=0.012). Additionally, in the lapatinib treated patient group, a decrease of serum levels of more than 20% after 4 cycles of chemotherapy showed a tendency to be associated with higher pCR rates (OR 7.7, 95% CI 0.8- 70, p=0.071). In contrast to the finding of the previous trial Geparquattro, this was not the case in the trastuzumab-treated patient group (p=n.s.). Conclusion: Results of this study demonstrate pre-chemotherapy sHER2 levels to be an independent predictor of response to NT with both trastuzumab and lapatinib treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-01.