Creating Better Utility of Test Results in EGFR-Mutated Metastatic NSCLC

By: Celeste L. Dixon
Posted: Wednesday, November 20, 2024

Clinicians may experience better overall utility of the Cobas^® EGFR mutation test (version 2) results in their surveillance of patients with metastatic non–small cell lung cancer (NSCLC), thanks to new research outcomes published in Scientific Reports. Geert A. Martens, MD, PhD, of Ghent University, Belgium, and colleagues said that currently, the test results generate semiquantitative index (SQI) values that correlate with mutant allele levels, but decision thresholds for patient-centric clinical use in NSCLC surveillance have been lacking, despite the test’s U.S. Food and Drug Administration approval as a qualitative liquid biopsy for actionable EGFR variants in NSCLC.

The team performed long-term circulating tumor DNA (ctDNA) monitoring of 20 patients, all with EGFR-mutated NSCLC, resulting in 155 on-treatment samples. They were able to identify optimal SQI intervals to predict or rule out disease progression within 12 weeks from sampling. With an AUC of 0.848, SQI showed significant diagnostic power, the authors stated.

“Our dual-threshold classifier of SQI 0/5/10 yielded informative results in 88% of blood draws with high negative predictive value,” they said. Specifically, SQI below 5 (63% of samples) had a 93% negative predictive value, whereas SQI above 10 (25% of samples) had a 69% positive predictive value.

The test demonstrated perfect agreement with sequencing and digital polymerase chain reaction, they continued. SQI values strongly (r = 0.910) correlated with mutant allele concentrations, with SQI of 5 and 10 corresponding to 6 to 9 (0.2%–0.3%) and 64 to 105 (1.1%–1.6%) mutant allele copies/mL (variant allele frequency), respectively.

“The clinical use of ctDNA for surveillance of metastatic cancers remains very limited,” stated Dr. Martens and co-investigators. “Clinicians lack guidance on reference values for ctDNA concentrations, so clinical actions can be coupled to a ctDNA concentration in an individual patient sample,” they stated.

Disclosure: The study authors reported no conflicts of interest.

Scientific Reports

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