Abstract 5187: Feasibility study of genomic biomarker profiling for patients with metastatic colorectal cancer

Abstract

Background: The adoption of NGS platforms and development of targeted oncology drugs have enabled matching of patients and drugs. The authors undertook an observational, clinical study to explore the feasibility and potential clinical benefits of an upfront approach to the genomic profiling of tumors from metastatic colorectal cancer (mCRC) patients. The study sought to determine the number of drug targetable genomic changes, which occur within mCRC patients including a comparison of patients who progress early versus late. Methods: The study targeted enrollment of 50 mCRC patients within the US Oncology Network followed by collection of archival FFPE samples and genomic testing. Sample collection and processing was performed at Quintiles Central Laboratories followed by testing and bioinformatic analysis at the Quintiles Genomic Laboratory. Genomic profiling was performed on the Ion Torrent PGM following enrichment of tumor DNA via the AmpliSeq Cancer Hotspot Panel v2 assay, enriching for hotspots within 50 cancer-related genes. Clinical annotation and reporting to the doctors was provided by NofOne. Basic demographic and clinical information was collected but formal disease monitoring and follow-up was not performed. Clinicians were asked to report the impact of the genomic test report on patient recommendations. Results: The study enrolled and profiled 51 stage IV mCRC patients from July 2013 to October 2013 from 18 sites in the US. Subjects were stratified by time to progression prior to entering the study. The study population was evenly distributed across early (< 1yr) and late progressors (> 1yr) with a median age of 62. Test turn-around time averaged 15 days. 98% of the bases sequenced in the genomic analysis reached the target coverage necessary to identify 5% variant frequency in the sample. Genomic variants associated with approved therapies in mCRC were observed in 7.8% of patients while 64.7% of patients had variants associated with approved therapies in other indications. 84.3% of patients had variant associated with open clinical trials. Of these 43 patients, 32 had multiple biomarkers with associated trials. Overall, more than 100 mutations were identified including alterations in KRAS, BRAF, EGFR, PIK3CA, GNAS, TP53, APC and other genes. The number of actionable mutations was not associated with progressor status. Doctors recommended clinical trials following profiling and reporting of genomic alterations in 15 out of the 51 patients (29%), Conclusions: The outcome of this observational study demonstrates the feasibility of rapid screening and reporting of NGS genomic results targeting actionable mutations in mCRC. The lack of an association between early and late progressors, suggests that a greater sample size will be required for future studies. The reported impact on clinician recommendations indicates the value of the results to inform treatment and clinical trial decisions. Citation Format: Bradley L. Smith, Philip Breitfeld, Jennifer Cubino, Victor Weigman, Donald P. Richards, Ki Y. Chung. Feasibility study of genomic biomarker profiling for patients with metastatic colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5187. doi:10.1158/1538-7445.AM2014-5187

A Systematic Literature Review and Meta-Analysis Describing the Prevalence of KRAS, NRAS, and BRAF Gene Mutations in Metastatic Colorectal Cancer

“…The studies included in our meta-analysis ranged in STROBE score from 5 to 22 with a mean of 15.2 and median of 16. All studies that received scores of less than 10, except Smith 2014 [46], were studies in which only the abstract was available. Therapies and combination regimens varied substantially across studies, with many studies not reporting specific treatments used by included patients.…”