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Guardant Health Liquid Biopsy Test Improves Gastrointestinal Cancer Clinical Trial Enrollment

NEW YORK – Analyzing circulating tumor DNA can both speed up and boost the enrollment of cancer patients into clinical trials, according to a new study focusing on gastrointestinal cancer. 

As hundreds or thousands of patients need to be screened for mutations of interest, identifying eligible patients can be a bottleneck for precision oncology studies. In a new study, researchers from Japan's National Cancer Center Hospital East compared circulating tumor DNA analysis to tissue genotyping for enrolling gastrointestinal patients into two large trials. One trial, SCRUM-Japan GOZILA, used the Guardant360 liquid biopsy to identify patients, while the other one, GI-SCREEN, relied on tissue genotyping. 

As the researchers reported in Nature Medicine on Monday, they were able to more quickly enroll a higher number of patients into a trial using the ctDNA approach. They further noted that liquid biopsy-based profiling uncovered a greater number of actionable mutations.

"The data demonstrate that genomic profiling by ctDNA analysis using the Guardant360 liquid biopsy has the advantage of shorter turnaround times and improved patient enrollment compared to tissue biopsy for clinical trials, without compromising treatment efficacy," first author Yoshiaki Nakamura from National Cancer Center Hospital East said in a statement.

For their analysis, the researchers built upon GI-SCREEN, a national GI cancer biomarker screening project that is part of the SCRUM-Japan network that aims to match patients across Japan to targeted therapy trials. As part of GI-SCREEN, patients undergo tissue-based DNA sequencing before or during systemic therapy. If they progress, they are enrolled in matched trials, but the need for tissue samples slows recruitment and screening time.

The researchers modeled their GOZILA approach on that method, but instead used ctDNA sequencing, specifically the Guardant360 test, to identify patients who were eligible for the trial. 

Between February 2015 and April 2019, GI-SCREEN enrolled 5,743 patients with advanced GI cancer, while GOZILA enrolled 1,787 patients between January 2018 and August 2019. CtDNA genotyping, the team reported, increased the relative proportion of enrolled patients by 132 percent and the absolute enrollment rate by 98 percent. In particular, while a mean 4.1 patients were enrolled each month by GI SCREEN, 8.1 were enrolled by liquid biopsy. 

Liquid biopsy testing also reduced the time from when patients underwent screening for study enrollment to enrolling in a clinical trial from a median 5.9 months to a median 1 month, an 83 percent reduction. Further, the median time from sample collection to trial enrollment fell from 20.2 months to 1.1 months.

The researchers also compared the objective response rates and progression-free survival among patients screened by these two approaches to see whether the testing method makes a difference. Both groups had similar objective response rates and progression-free survival, leading the researchers to conclude that ctDNA genotyping could reduce screening duration and increase trial enrollment without negatively affecting trial outcomes. 

At the same time, the researchers analyzed the genetic alterations that could be detected by liquid biopsy. The Guardant360 test analyzes 74 genes using next-generation sequencing. Among their patients, the researchers were able to identify multiple alterations, especially in KRAS, NRAS, BRAF, and PIK3CA. They additionally identified ERBB2, FGFR1-2, and MET amplifications and FGFR2-3, ALK, NTRK1, and RET fusions, as well as microsatellite instability.

For 232 GOZILA colorectal cancer patients for whom there were both ctDNA and tissue genotyping data available, the researchers noted a high overall concordance of results between the two approaches, reaching up to 100 percent for clonal alterations. Overall, though, ctDNA genotyping uncovered clinically relevant alterations at higher frequencies.

"These data complement other studies supporting the routine use of the Guardant360 test in personalized treatment decisions for patients with advanced cancer, and its potential to significantly accelerate the development and delivery of innovation in precision medicine to patients," AmirAli Talasaz, president of Guardant Health, said in a statement.