C Mayo-de-Las-Casas1, N Jordana-Ariza1, M Garzón-Ibañez1, A Balada-Bel1, J Bertrán-Alamillo1, S Viteri-Ramírez2, N Reguart3, M A Muñoz-Quintana4, P Lianes-Barragan5, C Camps6,7,8,9, E Jantús6,7,10, J Remon-Massip5, S Calabuig6,7,10, D Aguiar11, M L Gil1, N Viñolas3, A K Santos-Rodríguez12, M Majem13, B García-Peláez1, S Villatoro1, A Pérez-Rosado1, J C Monasterio1, E Ovalle1, M J Catalán1, R Campos1, D Morales-Espinosa2, A Martínez-Bueno2, M González-Cao2, X González14, I Moya-Horno14, A E Sosa15, N Karachaliou15, R Rosell16, M A Molina-Vila1. 1. Laboratory of Oncology, Pangaea Oncology, Quirón Dexeus University Hospital, Barcelona. 2. Dr Rosell Oncology Institute, Quirón Dexeus University Hospital, Barcelona. 3. Department of Medical Oncology, Hospital Clínic, Barcelona. 4. Department of Medical Oncology, Valencia Institute of Oncology, Valencia. 5. Department of Medical Oncology, Mataró Hospital, Mataró. 6. Molecular Oncology Laboratory, Fundación Investigación, Valencia General University Hospital, Valencia. 7. CIBERONC, Valencia. 8. Medical Oncology Department, Valencia General University Hospital, Valencia. 9. Department of Medicine, Universitat de València. 10. Department of Biotechnology, Universitat Politècnica de València. 11. Department of Medical Oncology, Hospital Dr Negrín of Gran Canaria, Las Palmas. 12. Department of Medical Oncology, Virgen de la Salud Hospital, Toledo. 13. Medical Oncology Service, Hospital de Sant Pau, Barcelona. 14. Dr Rosell Oncology Institute, General Hospital of Catalonia, Sant Cugat del Vallés. 15. Dr Rosell Oncology Institute, University Hospital Sagrat Cor, Barcelona. 16. Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Badalona, Spain.
Abstract
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/µl 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.
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/µl 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.
Authors: Charu Aggarwal; Jeffrey C Thompson; Taylor A Black; Sharyn I Katz; Ryan Fan; Stephanie S Yee; Austin L Chien; Tracey L Evans; Joshua M Bauml; Evan W Alley; Christine A Ciunci; Abigail T Berman; Roger B Cohen; David B Lieberman; Krishna S Majmundar; Samantha L Savitch; Jennifer J D Morrissette; Wei-Ting Hwang; Kojo S J Elenitoba-Johnson; Corey J Langer; Erica L Carpenter Journal: JAMA Oncol Date: 2019-02-01 Impact factor: 31.777
Authors: Julia Elzanowska; Laura Berrocal; Beatriz García-Peláez; Marta Vives-Usano; Beatriz Passos Sebo; Joana Maia; Silvia Batista; Jaakko Teppo; Markku Varjosalo; Maria Carolina Strano Moraes; Miguel Ángel Molina-Vila; Bruno Costa-Silva Journal: Cancers (Basel) Date: 2022-07-02 Impact factor: 6.575
Authors: Atocha Romero; Roberto Serna-Blasco; Cristina Alfaro; Estela Sánchez-Herrero; Miguel Barquín; María Carmen Turpin; Sofía Chico; Sandra Sanz-Moreno; Alejandro Rodrigez-Festa; Raquel Laza-Briviesca; Alberto Cruz-Bermudez; Virginia Calvo; Ana Royuela; Mariano Provencio Journal: Transl Lung Cancer Res Date: 2020-06