Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions
Por:
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
Publicada:
1 sep 2017
Resumen:
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.
Filiaciones:
Mayo-de-las-Casas, C:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Jordana-Ariza, N:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Garzon-Ibanez, M:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Balada-Bel, A:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Bertran-Alamillo, J:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Viteri-Ramirez, S:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst, Barcelona, Spain
Reguart, N:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Munoz-Quintana, MA:
Valencia Inst Oncol, Dept Med Oncol, Valencia, Spain
Lianes-Barragan, P:
Mataro Hosp, Dept Med Oncol, Mataro, Spain
Camps, C:
Valencia Gen Univ Hosp, Mol Oncol Lab, Fdn Invest, Valencia, Spain
CIBERONC, Valencia, Spain
Valencia Gen Univ Hosp, Med Oncol Dept, Valencia, Spain
Univ Valencia, Dept Med, Valencia, Spain
Jantus, E:
Valencia Gen Univ Hosp, Mol Oncol Lab, Fdn Invest, Valencia, Spain
CIBERONC, Valencia, Spain
Univ Politecn Valencia, Dept Biotechnol, Valencia, Spain
Remon-Massip, J:
Mataro Hosp, Dept Med Oncol, Mataro, Spain
Calabuig, S:
Valencia Gen Univ Hosp, Mol Oncol Lab, Fdn Invest, Valencia, Spain
CIBERONC, Valencia, Spain
Univ Politecn Valencia, Dept Biotechnol, Valencia, Spain
Aguiar, D:
Hosp Dr Negrin Gran Canaria, Dept Med Oncol, Las Palmas Gran Canaria, Spain
Gil, ML:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Vinolas, N:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Santos-Rodriguez, AK:
Virgen Salud Hosp, Dept Med Oncol, Toledo, Spain
Majem, M:
Hosp Sant Pau, Med Oncol Serv, Barcelona, Spain
Garcia-Pelaez, B:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Villatoro, S:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Perez-Rosado, A:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Monasterio, JC:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Ovalle, E:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Catalan, MJ:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Campos, R:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Morales-Espinosa, D:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst, Barcelona, Spain
Martinez-Bueno, A:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst, Barcelona, Spain
Gonzalez-Cao, M:
Quiron Dexeus Univ Hosp, Dr Rosell Oncol Inst, Barcelona, Spain
Gonzalez, X:
Gen Hosp Catalonia, Dr Rosell Oncol Inst, Sant Cugat Del Valles, Spain
Moya-Horno, I:
Gen Hosp Catalonia, Dr Rosell Oncol Inst, Sant Cugat Del Valles, Spain
Sosa, AE:
Univ Hosp Sagrat Cor, Dr Rosell Oncol Inst, Barcelona, Spain
Karachaliou, N:
Univ Hosp Sagrat Cor, Dr Rosell Oncol Inst, Barcelona, Spain
Rosell, R:
Germans Trias & Pujol Hlth Sci Inst & Hosp, Catalan Inst Oncol, Canc Biol & Precis Med Program, Badalona, Spain
Molina-Vila, MA:
Quiron Dexeus Univ Hosp, Lab Oncol, Pangaea Oncol, External Consultat Bldg,Room 1-7,C-Sabino Arana, Barcelona 08028, Spain
Bronze
|