Liquid Biopsy-based Test As Good As Tissue-based Test for Identifying Treatment for Lung Cancer

Single test could identify one prognostic and seven predictive biomarkers in blood

PHILADELPHIA – Guardant360, a liquid biopsy test that detects all guideline-recommended biomarkers in newly diagnosed metastatic non-small cell lung cancer (NSCLC), detected biomarkers at a rate similar to that of standard-of-care tissue genotyping tests but with a faster turn-around time, according to data presented during a media preview of the AACR Annual Meeting 2019, to be held March 29-April 3, in Atlanta.

“About 30 percent of lung cancers can now be treated with molecularly targeted therapies and the response rates using these treatments are much higher than with chemotherapy,” said Vassiliki Papadimitrakopoulou, MD, professor of medicine in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “But to identify patients who will benefit from these therapies, we need to ensure all patients are tested for these targetable mutations.”

A recent study showed that guideline-recommended testing was completed in only 8 percent of patients with NSCLC, Papadimitrakopoulou said, which means that most patients and their clinicians do not have all of the information available to make an informed therapy decision.

“Tissue biopsy-based tests are invasive, can have serious complications, are time-consuming, and the specimens are often inadequate to test for all the relevant mutations. Our study shows that Guardant360 test results can be obtained in about a week, are reliable, and in some respects a better alternative to the traditional tissue testing in ensuring guideline-complete molecular testing for all patients,” she noted.

This study examined whether Guardant360, a liquid biopsy test that utilizes cell-free tumor DNA (cfDNA) in blood, can be used to detect all seven guideline-recommended predictive biomarker mutations (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) and one prognostic biomarker mutation (KRAS), at the same rate as traditional tissue genotyping tests in a prospective, multi-center study called Noninvasive versus Invasive Lung Evaluation (NILE), in 282 patients with newly diagnosed advanced NSCLC.

At least one of the guideline-recommended biomarkers was detected in 60 patients using tissue-based tests alone. By adding Guardant360, the rate of detection increased by 48 percent, from 60 patients to 89 patients, which included those whose samples were negative by tissue (7), not tested (16), or did not have enough material (6) for the tissue-based tests.

The NILE study also found that the cfDNA test results of four biomarkers (EGFR, ALK, ROS1, BRAF), for which there are U.S. Food and Drug Administration-approved drugs, were concordant with the tissue-based test results, with a positive-predictive value of 100 percent.

“These findings should give confidence to oncologists to trust Guardant360 as a testing option for treatment selection in NSCLC patients,” Papadimitrakopoulou said.

The test turn-around time, defined as time from test order to final results, was a median of 9 days for Guardant360 versus a median of 15 days for tissue-based testing. “This differential is meaningful to patients and clinicians, and in my recent clinical experience, I can do an initial consult with a patient on a Monday and have them back in the office the following Monday to start treatment,” she noted.

“Advanced NSCLC is a uniformly deadly disease, therefore, getting patients on treatment as soon as possible is paramount,” Papadimitrakopoulou said. “Our results show that a highly sensitive and specific liquid biopsy should be part of the standard of care for these patients.”

Limitations of the study include that the liquid biopsy test was compared to a current standard-of-care tissue genotyping test and not the tissue-based next-generation sequencing test, and that the study results are only applicable to the Guardant360 test and not other liquid biopsy tests.

This study was funded by Guardant Health. Papadimitrakopoulou serves on the advisory boards of Nektar Therapeutics, AstraZeneca, Arrys Therapeutics, Merck, LOXO Oncology, Araxes Pharma, F. Hoffmann-La Roche, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, Novartis, Takeda, AbbVie, TRM Oncology, Tesaro, Exelixis, Nektar, Gritstone, and Arrys; has received CME speaker fees from F. Hoffmann-La Roche; and has received research support from Eli Lilly, Novartis, Merck, AstraZeneca, F. Hoffmann-La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, and Incyte.