New Assay Advances Personalized Therapy for Cancer Patients

Precision medicine attempts to direct treatment for a patient based on molecular alterations known to exist in the patient's disease and the treatment of patients with cancer has been at the center of the evolution for precision medicine studies.

This effort addresses therapeutic efficacy across multiple tissues, but also adds data as to the clinical value of broad-based screening panels versus disease-specific assays. A novel assay tailored for these trials is highly sensitive for detecting genetic mutations from a variety of tumor tissue and, for the first time, has been reproduced with accuracy by multiple clinical laboratories, laying the groundwork for future clinical utility.

A multidisciplinary team of scientists led by those at the Frederick National Laboratory for Cancer Research tested 186 samples and 12 cell lines at four different laboratories. Steps were taken to maximize standardization, including development of standard operating procedures, use of the same commercial assay and instruments, and face-to-face discussions. The National Cancer Institute's NCI-MATCH (Molecular Analysis for Therapy Choice) is a large, ongoing clinical trial that matches tumors to therapies based on the tumor's genetic characteristics.

The next generation sequencing (NGS) technology used in the trial was the Oncomine Cancer Panel assay and the Ion Personal Genome Machine is able to detect more than 4,000 pre-defined genomic variations across 143 genes, including single nucleotide variants (SNVs), insertions/deletions (indels), copy number variations (CNVs), and gene fusions. Levels of evidence were developed to select a subset of specific actionable genomic variants to be used for treatment matching.

The investigators report that the assay was highly sensitive, 96.98% for 265 known mutations, with 99.99% specificity. Since one feature of the NCI-MATCH trial is the wide variety of tumors examined, including solid tumors and lymphomas that no longer respond to standard therapy, the assay used must be able to analyze specimens from different tissues. Importantly, the NCI-MATCH NGS assay was able to accurately determine genetic abnormalities in biopsies from the pancreas, melanoma, bone, and skin.

Elizabeth R. Unger, PhD, MD, from the Centers for Disease Control and Prevention said, “The validation study reported is another step moving the field closer to the time when precision medicine will generate the expected benefits in improved clinical outcomes. Although the success of the NCI-MATCH trial cannot be assured, linking precision laboratories to precision medicine trials assures that data used for drug assignment will be reliable. Further, the use of a commercial platform and integrated analysis and reporting pipeline will greatly facilitate broader translation of any successes.” The study was published on February 7, 2017, in The Journal of Molecular Diagnostics.