Abstract PL01-02: The Breast International Group (BIG): Building on an accelerated path to tailored adjuvant cancer therapy

Abstract

Abstract The Breast International Group (BIG) : building an accelerated path to tailored adjuvant cancer therapy M. Piccart-Gebhart Today only 1 in 20 oncologic drugs that are tested in human subjects are ultimately shown to be efficacious and approved for widespread use. The vast majority of novel agents fail in advanced stages of clinical testing. Preliminary data suggests that the success rate is only marginally better for the family of targeted kinase inhibitors. After more than 40 years of clinical research in breast cancer, hormonal receptors and HER-2 status are the only predictive therapeutic markers that are routinely used in clinical decision-making. These markers have good negative predictive values but unsatisfactory positive predictive values. There is an exciting array of novel targeted therapies designed to inhibit aberrant pathways in the cancer cell currently in clinical testing. Many of these agents may only be effective in patients with specific molecular alterations. However, demonstrating differential activity in breast cancer subtypes and developing reliable predictive assays to select patients for novel targeted therapy remains a great challenge. The traditional model of establishing initial activity in patients with advanced refractory disease with subsequent retrospective biomarker discovery and validation in the adjuvant setting has failed to establish truly tailored therapies for use in the clinic. As a result, efforts are underway to move the discovery and validation of predictive biomarkers into earlier phases of drug development in the neoadjuvant setting. The NeoBIG program is being developed by the Breast International Group (BIG) to accelerate biomarker discovery and drug development in early breast cancer. Under this platform, a series of neo-adjuvant randomized phase II clinical trials (each with 300-600 patients) will be concomitantly launched to evaluate promising novel targeted therapies in different molecular breast cancer subtypes. Short-term endpoints, including pathological remission, proliferation markers, and imaging response, will be used to establish efficacy. These studies will integrate emerging technologies, such as genomics, proteomics, metabolomics, pharmacogenetics and functional imaging, to develop predictive markers of efficacy that can be validated in a subsequent adjuvant registration trial. In addition to addressing the need for accelerated development of more effective and less toxic therapies, modern trials should lead to an improved mechanistic understanding of the underlying biology of disease in specific patient populations. The NEO-BIG program will collaborate with basic science laboratories to improve our understanding of the biology of HER2 positive, triple negative and luminal B cancers. Citation Format: Martine J. Piccart-Gebhart. The Breast International Group (BIG): Building on an accelerated path to tailored adjuvant cancer therapy [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr PL01-02