PGX6475: PGx evaluation of HLA alleles with rash in lapatinib treated patients from TEACH (EGF105485)

Trial description: Lapatinib is approved for administration in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer (MBC) whose tumors overexpress HER2, and who have received prior cancer therapy, including anthracycline, a taxane, and trastuzumab. It is also approved for administration with aromatase inhibitors for the treatment of postmenopausal women with hormone receptor positive MBC that overexpress HER2 for whom hormonal therapy is indicated. In some markets, lapatinib is also approved in combination with paclitaxel for first-line treatment of HER2-positive MBC in patients for whom trastuzumab is not appropriate, or with trastuzumab for patients with hormone receptor-negative metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy. Rash is one of the most common adverse events observed with lapatinib treatment. It is a known class effect of agents that target the EGFR and/or HER2 receptor(s). Human leukocyte antigen (HLA) gene variants, have been identified with serious and moderate forms of drug-induced rash in other medicines. A genetic predictor could enable prospective identification of patients who have increased risk of lapatinib-induced rash and support focused action and management.The TEACH study (TYKERB® Evaluation After Chemotherapy) (EGF105485) is a large randomised, placebo controlled study of lapatinib treated patients with early stage, HER2 over-expressing breast cancer. The objective of this study is to determine if HLA genetic variants predict lapatinib-induced severe rash that, upon independent confirmation, could be clinically useful in identifying a high-risk subpopulation for focused management. This case control analysis will explore the impact of HLA genetic variation on lapatinib-induced rash using samples and clinical data collected during TEACH. Genetic data was generated during the conduct of EGF114471.TYKERB® is a registered trademark of the GlaxoSmithKline Group of Companies.