Abstract IA05: Immunoprevention of oral cancers

Abstract

Abstract Oral pre-malignant lesions (OPLs) are usually clinically characterized as leukoplakia or erythhroplakia, and confer an increased risk of oral cancer. Despite decades of clinical investigations with candidate chemopreventive agents such as 13-cis-retinoic acid, beta-carotene, fenretinide, green-tea extract, celecoxib, erlotinib, among others, a standard-of-care chemoprevention strategy for oral cancers has not yet been developed. Importantly, OPLs and oral cavity cancers are not related to HPV, thus HPV vaccines are not expected to be effective in this setting. One of the greatest challenges in managing patients with OPLs is determining risk for malignant transformation and need for intervention. To that end, retrospective and prospective studies have been completed by our group and others and demonstrate that LOH profiles (primarily at 13p14 and/or 9p21) in OPLs are associated with higher incidence of oral cancers. LOH is now considered the most robust prognostic marker of cancer risk in this setting, and these data now set the stage for development of clinical trials focused on molecularly-defined high risk groups of OPLs. Immune checkpoint blockade with antibodies directed at programmed cell death protein 1 (PD-1) has recently been successfully developed for the management of advanced head and neck squamous cell carcinomas, validating the importance of immune modulation in the progression of these invasive tumors. Given the favorable toxicity profile, there is interest in studying these agents for prevention of oral cancers in patients with high risk OPLs. In this presentation, we will review the data that support a role for immune surveillance and immune editing in the development of oral cancers, and describe the rationale and clinical trial design of the Immunoprevention of Oral Cancer (IPOC) study, the first randomized trial to evaluate the PD-1 inhibitor pembrolizumab for oral cancer prevention in patients with molecularly-defined high-risk OPLs. Citation Format: William N. William, Jr. Immunoprevention of oral cancers [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA05.