CONCORDANCE: A real-world evidence study to evaluate the concordance of detecting epidermal growth factor receptor (EGFR) mutation by circulating tumor DNA* versus tissue biopsy in patients with metastatic non-small cell lung cancer.

Background: Molecular tissue testing in non-small cell lung cancer (NSCLC) is done for the assessment of epidermal growth factor receptor (EGFR) mutation. EGFR mutation status is the basis for deciding the targeted treatment option for patients with metastatic NSCLC. The nonavailability of tissue samples and contraindications for biopsy pose a significant challenge. Hence, circulating tumor DNA (ctDNA) by liquid biopsy can be a viable alternative for NSCLC patients. Methods: This study was conducted at 15 sites across India. EGFR mutation testing from plasma was done as part of the study at the central laboratory by the next-generation sequencing (NGS) method, and EGFR mutation test results from tissue samples (done as part of routine practice) were recorded for all the patients. Results: Out of the total patients enrolled (N = 245), the majority (64.5%, n = 158) were men. The median age of patients was 58.0 (range: 26-84) years. The concordance between plasma and tissue testing was found to be 82.9% (95% confidence interval [CI]: 77.55, 87.45). The sensitivity and specificity of NGS were 68.4% (95% CI: 56.92, 78.37) and 90.1% [95% CI: 84.36, 94.21), respectively. Plasma testing detected 1.2% (n = 3) and tissue sample testing detected 2.4% (n = 6) positive status of exon 20 T790M EGFR mutation. Out of the total number of patients enrolled, 25 were tissue positive and plasma negative, while 16 were plasma positive and tissue negative. Conclusions: "> This real-world study in Indian patients suggests that plasma testing for EGFR mutation analysis is a viable diagnostic option in newly diagnosed advanced/metastatic NSCLC patients. The noninvasive plasma procedure in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies by providing clinicians with valuable insights into the patient's tumor mutation status. ClinicalTrials.gov Identifier: NCT03562819.