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Comprehensive cross‐platform comparison of methods for non‐invasive EGFR mutation testing: results of the RING observational trial

2020; Elsevier BV; Volume: 15; Issue: 1 Linguagem: Inglês

10.1002/1878-0261.12832

1878-0261

Atocha Romero, Eloísa Jantus‐Lewintre, Beatriz García‐Peláez, Ana Royuela, Amelia Insa, Patricia Cruz, Ana Collazo, J. Pérez Altozano, Óscar Juan, Pilar Díz, Manuel Cobo, Berta Hernández, Sergio Vázquez‐Estévez, Gretel Benítez, M. Guirado, Margarita Majem, Reyes Bernabé, A.L. Ortega Granados, Ana Blasco, Joaquim Bosch‐Barrera, José M. García, Jorge García, Santiago Viteri, Carlos García Girón, Bartomeu Massutí, Ana López Martín, Alejandro Rodríguez-Festa, Sílvia Calabuig-Fariñas, Miguel Ángel Molina‐Vila, Mariano Provencio,

Cancer therapeutics and mechanisms

Several platforms for noninvasive EGFR testing are currently used in the clinical setting with sensitivities ranging from 30% to 100%. Prospective studies evaluating agreement and sources for discordant results remain lacking. Herein, seven methodologies including two next-generation sequencing (NGS)-based methods, three high-sensitivity PCR-based platforms, and two FDA-approved methods were compared using 72 plasma samples, from EGFR-mutant non-small-cell lung cancer (NSCLC) patients progressing on a first-line tyrosine kinase inhibitor (TKI). NGS platforms as well as high-sensitivity PCR-based methodologies showed excellent agreement for EGFR-sensitizing mutations (K = 0.80-0.89) and substantial agreement for T790M testing (K = 0.77 and 0.68, respectively). Mutant allele frequencies (MAFs) obtained by different quantitative methods showed an excellent reproducibility (intraclass correlation coefficients 0.86-0.98). Among other technical factors, discordant calls mostly occurred at mutant allele frequencies (MAFs) ≤ 0.5%. Agreement significantly improved when discarding samples with MAF ≤ 0.5%. EGFR mutations were detected at significantly lower MAFs in patients with brain metastases, suggesting that these patients risk for a false-positive result. Our results support the use of liquid biopsies for noninvasive EGFR testing and highlight the need to systematically report MAFs.