Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions
Menée à partir d'échantillons sanguins prélevés sur 1 026 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cette étude évalue la possibilité d'utiliser l'ADN circulant pour détecter des mutations du gène EGFR et identifier les patients pouvant bénéficier d'un traitement par inhibiteur de tyrosine kinase du récepteur EGFR
Background : In a significant percentage of advanced 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) was retrospectively collected.
Results : Of 1033 NSCLC patients at presentation, 1026 were evaluable; 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 less than 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.
Annals of Oncology , résumé, 2016