Prospective analysis of liquid biopsies of advanced non-small cell lung cancer patients after progression to targeted therapies using GeneReader NGS platform
Por:
de las Casas, CM, Garzon-Ibanez, M, Jordana-Ariza, N, Viteri-Ramirez, S, Moya-Horno, I, Karachaliou, N, Yeste, Z, Campos, R, Villatoro, S, Balada-Bel, A, Garcia-Pelaez, B, Reguart, N, Teixido, C, Jantus, E, Calabuig, S, Aguado, C, Gimenez-Capitan, A, Roman-Llado, R, Perez-Rosado, A, Catalan, MJ, Bertran-Alamillo, J, Garcia-Roman, S, Rodriguez, S, Alonso, L, Aldeguer, E, Martinez-Bueno, A, Gonzalez-Cao, M, Hernandez, AA, Garcia-Mosquera, J, Gil, MD, Fernandez, M, Rosell, R and Molina-Vila, MA
Publicada:
1 ene 2019
Resumen:
Background: In a significant percentage of advanced non-small cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses at time to progression. We prospectively analyzed the appearance of genetic alterations associated with resistance in liquid biopsies of advanced NSCLC patients progressing to targeted therapies using the NGS platform.
Methods: A total of 24 NSCLC patients were included in the study, 22 progressing to tyrosine kinase inhibitors and two to other treatments. Liquid biopsies samples were obtained and analyzed using the GeneRead (TM) QIAact Lung DNA UMI Panel, designed to enrich specific target regions and containing 550 variant positions in 19 selected genes frequently altered in lung cancer tumors. Previously, a retrospective validation of the panel was performed in clinical samples.
Results: Of the 21 patients progressing to tyrosine kinase inhibitors with valid results in liquid biopsy, NGS analysis identified a potential mechanism of resistance in 12 (57%). The most common were acquired mutations in ALK and EGFR, which appeared in 8/21 patients (38%), followed by amplifications in 5/21 patients (24%), and KRAS mutations in one patient (5%). Loss of the p.T790M was also identified in two patients progressing to osimertinib. Three of the 21 (14%) patients presented two or more concomitant alterations associated with resistance. Finally, an EGFR amplification was found in the only patient progressing to immunotherapy included in the study.
Conclusions: NGS analysis in liquid biopsies of patients progressing to targeted therapies using the GeneReader platform is feasible and can help the oncologist to make treatment decisions.
Filiaciones:
de las Casas, CM:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Garzon-Ibanez, M:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Jordana-Ariza, N:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Viteri-Ramirez, S:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst IOR, Barcelona, Spain
Moya-Horno, I:
Gen Hosp Catalonia, Dr Rosell Oncol Inst IOR, QuironSalud Grp, Sant Cugat Del Valles, Spain
Karachaliou, N:
Univ Hosp Sagrat Cor, Dr Rosell Oncol Inst IOR, QuironSalud Grp, Barcelona, Spain
Yeste, Z:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Campos, R:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Villatoro, S:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Balada-Bel, A:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Garcia-Pelaez, B:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Reguart, N:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Teixido, C:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Jantus, E:
Hosp Gen Univ Valencia, Mol Oncol Lab, Fdn Invest, Valencia, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Univ Valencia, Dept Pathol, Valencia, Spain
Calabuig, S:
Hosp Gen Univ Valencia, Mol Oncol Lab, Fdn Invest, Valencia, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
Univ Valencia, Dept Pathol, Valencia, Spain
Aguado, C:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Gimenez-Capitan, A:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Roman-Llado, R:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Perez-Rosado, A:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Catalan, MJ:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Bertran-Alamillo, J:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Garcia-Roman, S:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Rodriguez, S:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Alonso, L:
Vall Hebron, Inst Oncol, Cellex Ctr, Barcelona, Spain
Aldeguer, E:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Martinez-Bueno, A:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst IOR, Barcelona, Spain
Gonzalez-Cao, M:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst IOR, Barcelona, Spain
Hernandez, AA:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst IOR, Barcelona, Spain
Garcia-Mosquera, J:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst IOR, Barcelona, Spain
Gil, MD:
Hosp Mateu Orfila, Menorca, Spain
Fernandez, M:
Univ Hosp Sagrat Cor, Dr Rosell Oncol Inst IOR, QuironSalud Grp, Barcelona, Spain
:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst IOR, Barcelona, Spain
Germans Trias & Pujol Hlth Sci Inst & Hosp, Canc Biol & Precis Med Program, Catalan Inst Oncol, Badalona, Spain
Molina-Vila, MA:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7, Barcelona 08028, Spain
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