Liquid Biopsy NonInferior to Tissue for Detection of Targetable Mutations in Advanced NSCLC

Significantly more genomic alterations can be detected with the Guardant360 liquid biopsy assay when used prior to tissue testing, results of a prospective study recently showed. Use of the assay allows patients with non–small cell lung cancer (NSCLC) to achieve similar response rates and progression-free survival (PFS) on treatment to those tested with tissue genotyping, Guardant Health, Inc, announced in a press release.¹

“Despite the ever-growing availability of life-changing targeted drugs for treating patients with advanced lung cancer, many continue to be treated with chemotherapy or immunotherapy because first-line treatments are made without conducting comprehensive genotyping first,” said the principal investigator of this study, Rafael Rossell, MD, PhD, chief medical officer and president of the Dr. Rosell Oncology Institute.

The report is based on recently published findings from a prospective study of 186 patients that performed a comparison of the Guardant360 liquid biopsy and standard-of-care (SOC) tissue genotyping in the frontline setting of advanced NSCLC. Notably, Guardant360 was not only concordant with tissue genotyping results, but also detected 23.6% more mutations when used prior to tissue biopsy.

Regarding the published report, Rossell stated: “This publication outlines further evidence that the Guardant Health liquid biopsy is very effective in uncovering, actionable genomic alterations, overcomes the challenges of tissue biopsies, and helps clinicians more easily customize treatments to improve the prognosis and survival of their patients.”

Using cell-free DNA (cfDNA), the liquid biopsy assay identified actionable mutations in 46 patients compared with the mutations found through tissue in 48 patients (P < .05), meeting the primary objective of noninferiority in the study. Altogether, 80.7% of patients who were tested with liquid biopsy had either a targetable mutation or a KRAS mutation. In comparison, mutations were identified in only 57.1% of patients when tissue biopsy was performed first. It was also noted that the positive predictive value for EGFR mutation detected by cfDNA was 100%. After the patients tested for mutations underwent treatment, the study found that targeted therapy resulted in a similar objective response rate and PFS regardless of whether patients were tested with liquid biopsy or tissue initially, and the outcomes were similar to previous reports of targeted therapies.²

Based on these findings, investigators confirmed that comprehensive cfDNA testing is noninferior to traditional tissue-based testing for the detection of biomarkers in patients with advanced NSCLC. The outcomes after targeted therapy for patients tested with liquid biopsy and tissue are similar, further confirming the noninferiority.

“Once again, the data show that our blood-first approach using our Guardant360 liquid biopsy has the advantage of increasing the number of patients receiving potentially life-changing targeted treatments without compromising treatment efficacy,” said Helmy Eltoukhy, CEO, Guardant Health, Inc, in a statement. “Sadly, research indicates that approximately 80 percent of advanced lung cancer patients do not receive comprehensive genotyping before starting treatment. I hope that with the recent FDA approval of our Guardant360 CDx liquid biopsy test, more clinicians will feel confident making the shift to liquid biopsies so we can reverse the serious trend of under genotyping that exists today.”

_References:

_{1. Head-to-head study shows guardant360 liquid biopsy outperforms tissue biopsy for comprehensive genomic profiling in advanced non-small cell lung cancer with similar outcomes. News release. Guardant Health, Inc. January 28, 2021. Accessed February 1, 2021. https://bit.ly/3px06j4}

_{2. Palmero R, Taus A, Viteri S, et al. Biomarker discovery and outcomes for comprehensive cell-free circulating tumor dna versus standard-of-care tissue testing in advanced non–small-cell lung cancer. JCO Precision Oncology. 2021;5:93-102. doi:10.1200/PO.20.00241}