Abstract SY40-02: Identification of novel modulators of response to immune checkpoint blockade in lung cancer patients through the marrying of clinical and genomic data

Abstract

Abstract The increasing use of comprehensive genomic profiling (CGP) in clinical practice for the genomic characterization of tumors is having an increasingly important impact on patients with cancer, empowering the rational use of both targeted therapies and immunotherapies and driving smarter, faster drug development. While some of the insights from clinical tumor sequencing have been realized, there remains a large gap between our understanding of the mutational landscape in cancer and its implication for patient treatment and outcomes. Furthermore, given the increasing subcategorization of cancer types by genetic lesion, efforts to understand the relationship between cancer genetics and clinical outcomes will require the use of large data sets. To date, the majority of these efforts have been largely confined to academic centers and limited by either number of patients or number of genes sequenced.Through a groundbreaking partnership between Foundation Medicine and Flatiron Health, a real-world dataset has been enabled, linking rich genomic and clinical outcomes data for over 20,000 oncology patients, the majority of whom have been treated in the community setting, in an HIPAA-compliant fashion. Within this cohort, longitudinal records from over 1,500 patients with NSCLC have been de-identified and consolidated in a research-grade clinico-genomic registry. These data include full somatic genomic records across the cohort, treatment histories, response to oncologic therapeutics, and multiple outcomes including PFS and OS, in addition to baseline clinical characteristics. The capabilities of these data and these novel methods of real-world observation are only beginning to be understood. Initial analytical validation has confirmed expected distributions of genomic findings and clinical characteristics, and early work still in progress had corroborated a number of known clinical and genomic correlates with survival, which will be presented. In a separate study marrying genomic, protein, and outcome data in a cohort of ~1,000 non–small lung cancer patients, modulators of response to immune checkpoint blockade were identified. These biomarkers include both immunosuppressors that explain why some patients with high tumor mutation burden (TMB) do not respond and immunogenic markers that explain why some patients with low TMB respond. Given the high cost and broadening use of immunotherapies, if validated in larger cohorts, these biomarkers will be important to more effectively stratify NSCLC patients by likelihood of response to immunotherapy. Citation Format: Phil Stephens. Identification of novel modulators of response to immune checkpoint blockade in lung cancer patients through the marrying of clinical and genomic data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY40-02. doi:10.1158/1538-7445.AM2017-SY40-02