Abstract IA11: Interactions between the genome and immune microenvironment in head and neck cancer

Abstract

Abstract Precision oncology is a term used to describe the attempt to match every cancer patient's tumor to the right drug or treatment, generally based on molecular or genomic features. At Memorial Sloan Kettering Cancer Center, the implementation of a targeted next-generation sequencing panel into routine clinical care for all patients with advanced tumors has allowed us to profile over 16,000 tumors in the past few years. The goal of such an approach has primarily been to match patients with recurrent and metastatic tumors to targeted therapies under the aegis of basket studies, and secondarily, to learn more about the unique biology of advanced cancers. This presentation will review the implementation of this precision oncology approach to patients with advanced head and neck cancer, particularly focused on squamous cell (HNSCC) and salivary carcinoma. The low number of targetable alterations in most head and neck tumor histologies has allowed for a modest degree of matching with targeted therapies. The program, however, has provided unprecedented insight into unique molecular features in recurrent/metastatic head and neck cancer. Some of the unique aspects discussed will be the genetic findings in aggressive HPV+ HNSCC and major subtypes of salivary cancer including adenoid cystic and salivary duct carcinoma. We are now entering an exciting era where we now understand that immunotherapy is highly active in HNSCC. This is largely the result of decades of basic immunologic investigation into identifying and targeting specific T cell checkpoint molecules. Phenomenal responses have been observed in patients with HNSCC, with overall response rates for heavily pretreated patients with metastatic disease in the 15-25% range. Unfortunately, many patients currently do not experience tumor responses. There is therefore a critical need to understanding patient and tumor features that may be predictive of response to immunotherapies such as immune checkpoint inhibitors. Immunogenomic approaches can provide insight into some of the aspects of tumor cells (such as mutation or neoantigen burden), or the tumor immune microenvironment (such as immune cell infiltration, measures of T cell activation, and expression of immunoregulatory molecules). Implementation of such approaches for HNSCC and salivary cancers in the context of a precision oncology approach to cancer care, can provide important insights to guide the next steps of clinical research. Multidimensional immunogenomic analyses can provide new insights into how the tumor genome and immune system interact with and shape one another. Citation Format: Luc G. T. Morris. Interactions between the genome and immune microenvironment in head and neck cancer [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 IA11.