ctDNA analysis reveals different molecular patterns upon disease progression in patients treated with osimertinib
dc.contributor.author | Romero, Atocha | |
dc.contributor.author | Serna-Blasco, Roberto | |
dc.contributor.author | Alfaro, Cristina | |
dc.contributor.author | Sánchez-Herrero, Estela | |
dc.contributor.author | Barquín, Miguel | |
dc.contributor.author | Turpín, María del Carmen | |
dc.contributor.author | Chico, Sofía | |
dc.contributor.author | Sanz-Moreno, Sandra | |
dc.contributor.author | Rodriguez-Festa, Alejandro | |
dc.contributor.author | Laza-Briviesca, Raquel | |
dc.contributor.author | Cruz-Bermudez, Alberto | |
dc.contributor.author | Calvo, Virginia | |
dc.contributor.author | Royuela, Ana | |
dc.contributor.author | Provencio, Mariano | |
dc.date.accessioned | 2021-09-02T08:43:56Z | |
dc.date.available | 2021-09-02T08:43:56Z | |
dc.date.issued | 2020 | |
dc.description.abstract | Background: 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 monitoring. | spa |
dc.description.extent | 468 KB | spa |
dc.identifier.doi | 10.21037/tlcr.2020.04.01 | spa |
dc.identifier.issn | 2218-6751 | spa |
dc.identifier.uri | http://hdl.handle.net/10641/2416 | |
dc.language.iso | eng | spa |
dc.publisher | Translational Lung Cancer Research | spa |
dc.relation.publisherversion | https://tlcr.amegroups.com/article/view/38250/html | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.accessRights | open access | spa |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Circulating tumor DNA (ctDNA) | spa |
dc.subject | Epidermal growth factor receptor (EGFR) | spa |
dc.subject | Non-small-cell lung cancer (NSCLC) | spa |
dc.subject | Osimertinib | spa |
dc.title | ctDNA analysis reveals different molecular patterns upon disease progression in patients treated with osimertinib | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dspace.entity.type | Publication |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- tlcr-09-03-532.pdf
- Size:
- 468.43 KB
- Format:
- Adobe Portable Document Format
- Description: