Two is better than one

GeneStrat, a genomic liquid biopsy test, utilizes circulating tumor nucleic acids from plasma, and is used by physicians to learn how to best treat patients with non-small cell lung cancer (NSCLC). In two presentations reported Aug. 8, Biodesix scientists described studies evaluating restriction enzymes for the analysis of cell-free DNA by droplet digital PCR (ddPCR).

At the Cancer Genomics Consortium Summer Meeting in Denver, Kristin Alexander, a Biodesix research associate, presented an overview of the product development process prior to commercialization of the blood-based test, which uses circulating RNA to test for tumor-derived transcripts resulting from the most common chromosomal rearrangements in NSCLC.

Approved therapies are available to treat NSCLC patients who test positive for the ALK, ROS1 and RET targets, she reported. An on-market study showed the GeneStrat RNA test result turnaround from a sample receipt at Biodesix took less than 48 hours in 81 percent of cases, and less than 72 hours in 96 percent of cases—time is critical, especially in treating late-stage cancer.

Biodesix research associate Amanda Weaver presented findings on the existing DNA process used for GeneStrat, stating that restriction enzymes were initially used in the development of the test, as recommended by Bio-Rad Laboratories, manufacturer of the ddPCR system. However, experiments showed that equivalent patient results were achieved without the use of restriction enzymes.

Weaver hypothesized that, as the GeneStrat test uses highly fragmented cell-free DNA (cfDNA), restriction enzymes were not necessary in the test workflow because cfDNA is already small enough to obviate the need for further digestion by restriction enzymes.

“The benefits of restriction enzyme removal include reduction in potential sources of PCR contamination and exclusion of unnecessary steps that can increase potential for human error,” Weaver states. “In addition, eliminating the use of restriction enzymes makes the testing process more efficient and saves time.”

The GeneStrat test also measures circulating tumor DNA and RNA with a highly-sensitive droplet digital PCR platform. The most recent publication supporting the clinical use of GeneStrat is the May 2017 Journal of Molecular Diagnostics paper entitled “Development and Clinical Utility of a Blood-Based Test Service for the Rapid Identification of Actionable Mutations in Non–Small Cell Lung Carcinoma.”

“Nearly 80 percent of cancer patients do not have genetic mutation results available at initial oncology consultation,” the journal article states. “Up to 25 percent of patients begin treatment before receiving their results. These factors hinder the ability to pursue optimal treatment strategies. This study validates a blood-based genome-testing service that provides accurate results within 72 hours.”

Test development included method and clinical validation using samples from donors with or without cancer, the authors state. Clinical sensitivity and specificity for each variant ranged from 78.6 percent to 100 percent and 94.2 percent to 100 percent, respectively.

“We detected 10.5 percent mutations for EGFR sensitizing, 13.8 percent mutations for EGFR resistance, 13.2 percent mutations in KRAS and 2 percent mutations for EML4-ALK fusion,” the authors state. “This rapid, highly sensitive and actionable blood-based assay service expands testing options and supports faster treatment decisions.”

The VeriStrat test is the focal point of a study published July 10 in the journal Lung Cancer that involved a retrospective analysis of the data from the Phase 3 LUX Lung 8 trial with afatinib (Gilotrif) and the Biodesix VeriStrat test.

Published findings show that the Biodesix VeriStrat test is prognostic for outcomes in patients with squamous cell carcinoma of the lung who are treated with afatinib. Patients with VeriStrat-Good (VS-G) classification had superior survival outcomes on afatinib compared to erlotinib.

“The present data clearly show that EGFR-TKI therapy is useful for VeriStrat-Good patients and that afatinib confers significantly better survival than erlotinib, with median overall survival of 11.5 months versus 8.9 months for the VS-G patients,” states Dr. Glenwood D. Goss, a professor of Medicine of the University of Ottawa. “While further validation studies are needed, these survival data compare very favorably with other therapies that are currently available for the second-line treatment of patients with squamous cell carcinoma of the lung.”

Biodesix CEO David Brunel states: “Using a diagnostic test such as VeriStrat can improve the likelihood that patients will receive optimal therapy. While immunotherapies are the preferred standard of care in second line, and an increasingly important consideration in the first line, they only provide durable benefit in a subset of patients, and many patients progress. Based on this study, afatinib has greater activity in VS-G patients.”