Mutational landscape of metastatic cancers discovered from prospective clinical sequencing at community practice cancer program

Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that can be therapeutically targeted. We present an analysis of the results of comprehensive genomic profiling (CGP) from a large series of patients assayed in the setting of a community practice cancer network. Methods: IRB-approved analysis of pts assayed with CGP using hybrid-capture NGS based CGP assays were performed on 6,177 pts with advanced cancer during the course of clinical care for the purpose of making therapy decisions, with GA suggesting the latter labeled as clinical relevant. Three genomic platforms were utilized, FoundationOne (315 genes, 89% of tests), FoundationOne-Heme (405 genes, 6%) and FoundationAct, (62 genes, 5%) Results: From 01-2013 to 09-2017, clinical samples from 6,177 pts (6496 CGP assays) with advanced cancer underwent CGP. Median age was 56 years (range, 18-94), 61% of pts were female, 68% were Caucasian. The most common tumor types studies were breast (18%), colorectal (15%), lung (14%), gynecological (11%) and unknown cancer (10%). GA were identified in 94% (5839/6496) of cases, and GA were classified as clinically relevant (47%)/not clinical relevant (52.6%). The most frequent clinically relevant GA were in KRAS (23%) and PIK3CA (15%). The most common genomic alterations were amplification (32%). Treatment history for a large subset of patients (4490) showed that 23% (1169/4490) of pts were ordered a genomically-matched treatment, 57% (662/1169) of which were tied to an FDA approved agent in a different tumor type, and 15% of which (178/1169) were referred to a matched mechanism driven clinical trial. With the access to TAPUR the frequency of matched treatment for clinical trials increased over time from 2013 to 2017. Conclusions: In a large series of diverse patients assayed with CGP in the community setting, 23% of patients received matched treatment, which was predominantly targeted therapy. The increasing frequency of matching treatment over time and the advent of immunotherapy and matching with PDL1 and tumor mutational burden may further increase the proportion of this population. Future analysis will explore outcomes for this subset of pts. Legal entity responsible for the study: Ricardo H. Alvarez. Funding: Has not received any funding. Disclosure: J. Elvin, P. Reddy, V.A. Miller, S.M. Ali: Employee, stock owner: Foundation Medicine. All other authors have declared no conflicts of interest.