PP255 Epigenetic Profile Predicts Response To Immunotherapy In Patients With Non-Small-Cell Lung Cancer: An Early Assessment

Abstract

IntroductionEpigenetics is an innovative discipline that aims to provide biomarkers to aid in early diagnosis, patient risk classification, or outcome prediction. The identification of therapeutic targets is of particular interest in cancer therapy for selecting groups of patients who may benefit most from an intervention. Understanding the relationships between the immune system and tumor cells has led to new immunotherapy-based therapies that provide a promising alternative to conventional cancer therapies. The aim of this study was to conduct an early assessment of a novel epigenetic signature (EPIMMUNE) that could predict response to programmed cell death protein 1 (PD-1) inhibitor immunotherapy in patients with non-small cell lung cancer (NSCLC).MethodsWe identified the novel epigenetic signature EPIMMUNE through the Early Awareness and Alert System, “SINTESIS-new technologies” of the Agencia de Evaluación de Tecnologías Sanitarias in Spain (AETS-ISCIII). A literature search of PubMed, Embase, the Web of Science, the Trip database, the International Clinical Trials Registry Platform, ClinicalTrials.gov, The Cochrane Library, and the Centre for Reviews and Dissemination databases was conducted. Clinical studies on EPIMMUNE published in English or Spanish up to August 2019 were reviewed.ResultsOnly one retrospective study was found. Identification of EPIMMUNE was accomplished through interrogation of the DNA methylation status of CpG sites in 142 samples from adult patients with NSCLC who were treated with PD-1 inhibitors. EPIMMUNE was defined by 301 CpG sites whose methylation status was significantly associated with clinical response (progression-free and overall survival). No studies assessing the long-term clinical utility, impact on therapeutic decision making, or economic implications of EPIMMUNE were found.ConclusionsThe EPIMMUNE signature could provide an accurate and valid biomarker for identifying patients with NSCLC who may benefit from treatment with PD-1 inhibitors. However, the technology is under development, and there is only a single study on detecting the EPIMMUNE epigenetic profile and identifying the DNA methylation profiles associated with increased survival after PD-1 inhibitor therapy. More diagnostic accuracy studies and prospective, long-term trials are needed to evaluate the clinical impact this technology may have on therapeutic decision making. Given the limited evidence available, further research is needed before the technology can be disseminated.