Biomarker Data from KATHERINE: A Phase III Study of Adjuvant Trastuzumab Emtansine versus Trastuzumab in Patients with Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer

KATHERINE (NCT01772472) compared adjuvant trastuzumab emtansine (T-DM1) and trastuzumab following neoadjuvant HER2-targeted therapy and chemotherapy in patients with residual invasive breast cancer at surgery. Exploratory analyses investigated the relationship between invasive disease-free survival (IDFS) and HER2 protein expression/gene amplification, PIK3CA hotspot mutations, and gene expression of HER2, PD-L1, CD8, predefined immune signatures, and Prediction Analysis of Microarray 50 intrinsic molecular subtypes. T-DM1 improved IDFS versus trastuzumab across major biomarker subgroups. High versus low HER2 gene expression in the surgical residual tumor sample was associated with worse outcomes with trastuzumab (HR, 2.02; 95% confidence interval [CI], 1.32–3.11), but IDFS with T-DM1 was independent of HER2 expression level (HR, 1.01; 95% CI, 0.56–1.83). Low PD-L1 gene expression in the surgical residual tumor sample was associated with worse outcomes with trastuzumab (HR, 0.66; 95% CI, 0.44–1.00), but not T-DM1 (HR, 1.05; 95% CI, 0.59–1.87). PIK3CA mutations were not prognostic.EGA study EGAS00001006229