Clinical implementation of whole genome multi-omics analyses for patients with refractory cancers.

Abstract

1531 Background: Relative lack of prior success of genomic technology has been a function of suboptimal target detection and poor timely implementation. We set out to improve patient access to targeted therapy through use of whole genome sequencing (WGS) to optimize targets and operational implementation to identify clinical trials and secure off-label drugs. Methods: We performed a retrospective analysis of our first 100 patients (Feb-Nov 2016) with metastatic disease whose tumors and matched blood were analyzed using whole genome (WGS) and transcriptome sequencing, as well as targeted proteomic analysis in a CLIA setting (NantOmics). Most common tumor types were Colorectal (20%), Breast (15%), and Ovarian (10%). Patients were seen in dedicated precision genomics clinics with results reviewed by a multi-disciplinary molecular tumor board. A dedicated service line with staff to match patients to clinical trials, medication acquisition, and genetic counseling for germline findings was provided. Results: 85% of patients had a finding either on WGS or proteomic analysis that pointed to an FDA approved drug or clinical trial. Common findings included: mutations in the PI3K pathway (15%), BRCA1&2/ATM (15%), and cell cycle genes (11%). Other markers of note include: HER2, TMB/MSI for immune checkpoint therapy, IDH1/2, and MET. WGS also enabled identification of rare actionable findings, particularly translocations, and viral integration for trials requiring HPV-positivity. Cancer predisposition germline findings were observed in 3 patients. Of the 85 patients with actionable findings, 22 went on to be treated with a genomically-directed agent, 13 did not follow recommendations or were sent to hospice, 4 were lost to follow-up, and 46 still remain on their therapy prescribed prior to sequencing. Conclusions: A higher proportion of patients in our program went on to be treated with a genomically-directed agent than previously reported in the literature secondary to comprehensive whole genome multi-omics profiling and a clinical service line dedicated to medication acquisition and matching to clinical trials.