Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions

Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patien...

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Detalles Bibliográficos
Autores: Mayo-de-las-Casas, C, Jordana-Ariza, N, Garzon-Ibanez, M, Balada-Bel, A, Bertran-Alamillo, J, Viteri-Ramirez, S, Reguart, N, Munoz-Quintana, MA, Lianes-Barragan, P, Camps, C, Jantus, E, Remon-Massip, J, Calabuig, S, Aguiar, D, Gil, ML, Vinolas, N, Santos-Rodriguez, AK, Majem, M, Garcia-Pelaez, B, Villatoro, S, Perez-Rosado, A, Monasterio, JC, Ovalle, E, Catalan, MJ, Campos, R, Morales-Espinosa, D, Martinez-Bueno, A, Gonzalez-Cao, M, Gonzalez, X, Moya-Horno, I, Sosa, AE, Karachaliou, N, Rosell, R, Molina-Vila, MA
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p6345
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6345
Access Level:acceso abierto
Palabra clave:EGFR mutations
NSCLC
tyrosine-kinase inhibitors (TKIs)
liquid biopsy
Descripción
Sumario:Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected. Results: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had <10 pg mutated genomes/ml with allelic fractions below 0.25%. Patients treated first line with TKIs based exclusively on EGFR positivity in blood had an ORR of 72% and a median PFS of 11 months. Of 105 patients screened after progression to EGFR-TKIs, sensitizing mutations were found in 56.2% and the p.T790M resistance mutation in 35.2%. Conclusions: Large-scale EGFR testing in the blood of unselected advanced NSCLC patients is feasible and can be used to select patients for targeted therapy when testing cannot be done in tissue. The characteristics and clinical outcomes to TKI treatment of the EGFR-mutated patients identified are undistinguishable from those positive in tumor.

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