BACKGROUND: Circulating cell-free DNA (cfDNA) may help understand the molecular response to pharmacologic treatment and provide information on dynamics of clonal heterogeneity. Therefore, this study evaluated the correlation between treatment outcome and activating EGFR mutations (act-EGFR) and T790M in cfDNA in patients with advanced NSCLC given osimertinib. METHODS: Thirty-four NSCLC patients resistant to first/second-generation EGFR-TKIs, positive for both act-EGFR and T790M in cfDNA at the time of progression were enrolled in this study. Plasma samples were obtained at osimertinib baseline and after 3 months of therapy; cfDNA was analyzed by droplet digital PCR and results were expressed as mutant allele frequency (MAF). RESULTS: At baseline, act-EGFR MAF was significantly higher than T790M (p < 0.0001). act-EGFR MAF and T790M/act-EGFR MAF ratio were significantly correlated with disease response (p = 0.02). Cut-off values of act-EGFR MAF and T790M/act-EGFR ratio of 2.6% and 0.22 were found, respectively. The PFS of patients with act-EGFR MAF of > 2.6% and < 2.6%, were 10 months vs. not reached, respectively (p = 0.03), whereas patients with T790M/act-EGFR ≤ 0.22 had poorer PFS than patients with a value of > 0.22 (6 months vs. not reached, respectively, p = 0.01). CONCLUSION: act-EGFR MAF and T790M/act-EGFR MAF ratio are potential markers of outcome in patients treated with osimertinib.

The amount of activating EGFR mutations in circulating cell-free DNA is a marker to monitor osimertinib response

Del Re, Marzia
Primo
;
Rofi, Eleonora;Restante, Giuliana;Valleggi, Simona;Crucitta, Stefania;Petrini, Iacopo
Penultimo
;
Danesi, Romano
Ultimo
Writing – Original Draft Preparation
2018

Abstract

BACKGROUND: Circulating cell-free DNA (cfDNA) may help understand the molecular response to pharmacologic treatment and provide information on dynamics of clonal heterogeneity. Therefore, this study evaluated the correlation between treatment outcome and activating EGFR mutations (act-EGFR) and T790M in cfDNA in patients with advanced NSCLC given osimertinib. METHODS: Thirty-four NSCLC patients resistant to first/second-generation EGFR-TKIs, positive for both act-EGFR and T790M in cfDNA at the time of progression were enrolled in this study. Plasma samples were obtained at osimertinib baseline and after 3 months of therapy; cfDNA was analyzed by droplet digital PCR and results were expressed as mutant allele frequency (MAF). RESULTS: At baseline, act-EGFR MAF was significantly higher than T790M (p < 0.0001). act-EGFR MAF and T790M/act-EGFR MAF ratio were significantly correlated with disease response (p = 0.02). Cut-off values of act-EGFR MAF and T790M/act-EGFR ratio of 2.6% and 0.22 were found, respectively. The PFS of patients with act-EGFR MAF of > 2.6% and < 2.6%, were 10 months vs. not reached, respectively (p = 0.03), whereas patients with T790M/act-EGFR ≤ 0.22 had poorer PFS than patients with a value of > 0.22 (6 months vs. not reached, respectively, p = 0.01). CONCLUSION: act-EGFR MAF and T790M/act-EGFR MAF ratio are potential markers of outcome in patients treated with osimertinib.
Del Re, Marzia; Bordi, Paola; Rofi, Eleonora; Restante, Giuliana; Valleggi, Simona; Minari, Roberta; Crucitta, Stefania; Arrigoni, Elena; Chella, Antonio; Morganti, Riccardo; Tiseo, Marcello; Petrini, Iacopo; Danesi, Romano
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/933920
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