A new comprehensive next generation sequencing (NGS) platform is more likely than targeted NGS platforms to identify clinically relevant and actionable molecular alterations in metastatic cancers, according to research that will be presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).
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Physicians often utilize NGS platforms in the management of metastatic cancer in adults to identify tumor genomic alterations that could serve as therapeutic targets. Previous biomarker-driven clinical trials—including NCI-Molecular Analysis for Therapy Choice (MATCH) and Targeted Agent and Profiling Utilization Registry (TAPUR)—have provided results that support the use of NGS platforms in clinical practice.
Erin Frances Cobain, MD, University of Michigan Health System (Ann Arbor, MI), and colleagues analyzed sequencing data of adult patients with metastatic solid tumors for clinically relevant genomic alterations. Patients underwent biopsy for whole exome and transcriptome sequencing of their tumors, which were then matched to normal samples through the Michigan Oncology Sequencing Center (Mi-Oncoseq). Identified alterations were reviewed and grouped according to their clinical relevance. Additionally, researchers classified alterations as either identifiable or not identifiable by utilizing a commercially available NGS assay.
Approximately 500 patients with diverse tumor lineage were included in the study from 2011 to 2015.
Results of the analysis showed that genomic alterations identified by Mi-Oncoseq provided evidence in favor of further enrollment in a clinical trial in 72% of cases (n = 360). Those patients who received therapy as a result of NGS findings increased over time (5% in 2012 vs 11% in 2015). Eleven percent of patients (n = 55) harbored a pathogenic germline variant that increased their risk of cancer, unbeknown to them prior to study entry.
Authors of the study also noted that multiple patients exhibited clinically relevant molecular alterations—including pathogenic germline variant and activating/deleterious gene fusions—that were identifiable by utilizing Mi-Oncoseq but not identifiable by utilizing targeted NGS assays.
Authors concluded that comprehensive NGS is capable of identifying significantly more actionable genomic alterations in the majority of adult patients with metastatic cancer than targeted NGS platforms. Furthermore, comprehensive NGS was able to identify unanticipated pathogenic germline variants of clinical important for patients and their families in the study.
“We detected an unexpected pathogenic germline variant in many more of our patients than anticipated, which perhaps serves as an indicator that there may be germline variants at a higher frequency than generally believed among patients with metastatic tumors. This has potential biological implications for family members of the given patient," said Dr Cobain in an interview.—Zachary Bessette
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