Abstract 4495: Development and clinical application of an integrative genomic approach to personalized cancer therapy

Abstract

Abstract We implemented a personalized cancer therapy (PCT) program in a clinical setting, applying an integrative genomics approach to maximally elucidate the complexity of each tumor. For patients in the study, we performed whole exome sequencing and SNP microarrays on tumor and patient-matched normal samples, as well as RNA sequencing on available frozen samples, to identify somatic mutations, copy number alterations, gene fusions, and gene expression alterations in the tumor. Ion AmpliSeq Cancer Hotspot Panel v2 (CHPv2) was used to ensure high sensitivity in cancer mutation hotspots. Genomics results were integrated with cancer knowledge databases and for each cancer type a specific workflow was developed to optimize data interpretation. We returned genomics findings to 46 patients and their physicians, characterizing somatic alterations and predicting drug response, toxicity, and prognosis. Mean 17.3 cancer-relevant somatic mutations per patient were identified, 13.3-, 6.9-, and 4.7-fold more than could have been detected using CHPv2, Oncomine Cancer Panel (OCP), and FoundationOne, respectively. Our approach delineated the underlying genetic drivers at the pathway level and provided meaningful predictions of therapeutic efficacy and toxicity. Actionable alterations were found in 91% of patients (mean 4.9 per patient, including somatic mutations, copy number alterations, gene expression alterations, and germline variants), a 7.5-fold, 2.0-fold, and 1.9-fold increase over what could have been uncovered by CHPv2, OCP, and FoundationOne, respectively. The findings altered the course of treatment in 4 cases. These results show that a comprehensive, integrative genomic approach as outlined above significantly enhanced genomics-based personalized cancer therapy strategies. Citation Format: Rong Chen. Development and clinical application of an integrative genomic approach to personalized cancer therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4495.