Evolution and Clinical Impact of EGFR Mutations in Circulating Free DNA in the BELIEF Trial
| Autor: | Niki Karachaliou, Zoi Tsourti, Bartomeu Massuti, Santiago Ponce Aix, Martin Früh, Miklos Pless, Paolo Bidoli, Núria Jordana-Ariza, Ariadna Balada-Bel, H. Roschitzki-Voser, Enriqueta Felip, Solange Peters, Mónica Garzón-Ibáñez, Roswitha Kammler, Ramon Palmero, Sinead Cuffe, Clara Mayo-de-las-Casas, Rafael Rosell, Sanjay Popat, Enric Carcereny, M.A. Molina-Vila, Oliver Gautschi, Beatriz García-Peláez, Rolf A. Stahel, Urania Dafni, Alessandra Curioni Fontecedro |
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| Přispěvatelé: | Molina-Vila, M, Stahel, R, Dafni, U, Jordana-Ariza, N, Balada-Bel, A, Garzón-Ibáñez, M, García-Peláez, B, Mayo-de-Las-Casas, C, Felip, E, Fontecedro, A, Gautschi, O, Peters, S, Massutí, B, Palmero, R, Aix, S, Carcereny, E, Früh, M, Pless, M, Popat, S, Cuffe, S, Bidoli, P, Kammler, R, Roschitzki-Voser, H, Tsourti, Z, Karachaliou, N, Rosell, R, University of Zurich, Stahel, Rolf A |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
EGFR mutations in blood
NSCLC Survival cfDNA 0301 basic medicine Pulmonary and Respiratory Medicine medicine.medical_specialty Lung Neoplasms genetic structures Survival Bevacizumab EGFR 610 Medicine & health NSCLC Gastroenterology Disease-Free Survival 03 medical and health sciences Exon 0302 clinical medicine Internal medicine medicine Humans In patient cfDNA neoplasms Protein Kinase Inhibitors business.industry EGFR mutations in blood DNA Confidence interval respiratory tract diseases ErbB Receptors 030104 developmental biology Real-time polymerase chain reaction Oncology Circulating free DNA Egfr mutation 2740 Pulmonary and Respiratory Medicine 030220 oncology & carcinogenesis Mutation 10032 Clinic for Oncology and Hematology 2730 Oncology Erlotinib Neoplasm Recurrence Local business Cell-Free Nucleic Acids medicine.drug |
| Zdroj: | Journal of Thoracic Oncology r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Universidad de Alicante (UA) JOURNAL OF THORACIC ONCOLOGY r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante instname r-IGTP: Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol Institut de Recerca Germans Trias i Pujol (IGTP) |
| ISSN: | 1556-1380 1556-0864 |
| Popis: | Introduction: Longitudinal evaluation of mutations in blood samples was a prespecified secondary objective in the BELIEF trial of erlotinib and bevacizumab in advanced EGFR-positive NSCLC. Here, we report the testing results and explore the correlation of EGFR status in blood with clinical outcomes. Methods: Blood samples were prospectively collected from patients at baseline, at response evaluation, and at progression and sent to a central laboratory. Circulating free DNA was purified and EGFR mutations were analyzed with a validated real-time quantitative polymerase chain reaction assay. Results: EGFR exon 19/21 mutations were detected in 55 of 91 baseline blood samples (60.4%) and correlated with a significantly worse progression-free survival: 11.4 months (95% confidence interval [CI]: 9.0-14.8 mo) for the patients who were positive versus 22.9 months (95% CI: 9.5-33.9 mo) for those who were negative (log-rank p = 0.0020). Among the 74 samples at response, exon 19/21 mutations were detected only in three samples (4.1%). In contrast, 29 of 58 patients (50.0%) were exon 19/21 positive at progression and showed a significantly worse median overall survival of 21.7 months (95% CI: 17.0-30.9 mo) compared with 37.4 months (95% CI: 22.6-53.1 mo) for those who were negative (log-rank p = 0.011). Blood samples at the three time points were available for 48 patients. Of those, among 14 exon 19/21 EGFR-negative at presentation, 13 (93%) were persistently negative for the sensitizing mutations after progression and the p.T790M could only be detected in the blood of two patients. Conclusions: Longitudinal testing of EGFR mutations in blood can offer valuable clinical information. In patients of the BELIEF study, detection of EGFR mutations in circulating free DNA at presentation was associated with shorter progression-free survival, whereas positivity at progression correlated with shorter overall survival. Finally, patients negative in blood at presentation were almost invariably negative at relapse. (C) 2019 Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. |
| Databáze: | OpenAIRE |
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