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dc.contributor.authorRomero, Atocha
dc.contributor.authorSerna-Blasco, Roberto
dc.contributor.authorAlfaro, Cristina
dc.contributor.authorSánchez-Herrero, Estela
dc.contributor.authorBarquín, Miguel
dc.contributor.authorTurpín, María del Carmen 
dc.contributor.authorChico, Sofía
dc.contributor.authorSanz-Moreno, Sandra
dc.contributor.authorRodriguez-Festa, Alejandro
dc.contributor.authorLaza-Briviesca, Raquel
dc.contributor.authorCruz-Bermudez, Alberto
dc.contributor.authorCalvo, Virginia
dc.contributor.authorRoyuela, Ana
dc.contributor.authorProvencio, Mariano
dc.description.abstractBackground: Several clinical trials have demonstrated the efficacy and safety of osimertinib in advanced nonsmall-cell lung cancer (NSCLC). However, there is significant unexplained variability in treatment outcome. Methods: Observational prospective cohort of 22 pre-treated patients with stage IV NSCLC harboring the epidermal growth factor receptor (EGFR) p.T790M resistance mutation and who were treated with osimertinib. Three hundred and twenty-six serial plasma samples were collected and analyzed by digital PCR (dPCR) and next-generation sequencing (NGS). Results: The median progression-free survival (PFS), since the start of osimertinib, was 8.9 [interquartile range (IQR): 4.6–18.0] months. The median treatment durations of sequential gefitinib + osimertinib, afatinib + osimertinib and erlotinib + osimertinib treatments were 30.1, 24.6 and 21.1 months, respectively. The p.T790M mutation was detected in 19 (86%) pre-treatment blood samples. Undetectable levels of the original EGFR-sensitizing mutation after 3 months of treatment were associated with superior PFS (HR: 0.2, 95% CI: 0.05–0.7). Likewise, re-emergence of the original EGFR mutation, alone or together with the p.T790M mutation was significantly associated with shorter PFS (HR: 8.8, 95% CI: 1.1–70.7 and HR: 5.9, 95% CI: 1.2–27.9, respectively). Blood-based monitoring revealed three molecular patterns upon progression to osimertinib: sensitizing+/T790M+/C797S+, sensitizing+/T790M+/C797S–, and sensitizing+/T790M–/ C797S–. Median time to progression in patients showing the triplet pattern (sensitizing+/T790M+/C797S+) was 12.27 months compared with 4.87 months in patients in whom only the original EGFR sensitizing was detected, and 2.17 months in patients showing the duplet pattern (sensitizing+/T790M+). Finally, we found that mutations in exon 545 of the PIK3CA gene were the most frequent alteration detected upon disease progression in patients without acquired EGFR-resistance mutations. Conclusions: Different molecular patterns identified by plasma genotyping may be of prognostic significance, suggesting that the use of liquid biopsy is a valuable approach for tumor
dc.publisherTranslational Lung Cancer Researchspa
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.subjectCirculating tumor DNA (ctDNA)spa
dc.subjectEpidermal growth factor receptor (EGFR)spa
dc.subjectNon-small-cell lung cancer (NSCLC)spa
dc.titlectDNA analysis reveals different molecular patterns upon disease progression in patients treated with osimertinibspa
dc.description.extent468 KBspa

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Atribución-NoComercial-SinDerivadas 3.0 España
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