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Resistance profile of osimertinib in pre-treated patients with EGFR T790M-mutated non-small cell lung cancer

2021-05-06Journal article Open access
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dc.contributor.authorFernandes, Maria Gabriela O.
dc.contributor.authorSousa, Catarina
dc.contributor.authorJacob, Maria
dc.contributor.authorAlmeida, Leonor
dc.contributor.authorSantos, Vanessa
dc.contributor.authorAraújo, David
dc.contributor.authorBastos, Hélder Novais
dc.contributor.authorMagalhães, Adriana
dc.contributor.authorCirnes, Luís
dc.contributor.authorMoura, Conceição Souto
dc.contributor.authorQueiroga, Henrique
dc.contributor.authorCruz-Martins, Natália
dc.contributor.authorHespanhol, Venceslau
dc.date.accessioned2024-02-21T12:52:20Z
dc.date.available2024-02-21T12:52:20Z
dc.date.issued2021-05-06
dc.description.abstract Osimertinib efficacy in pre-treated patients with epidermal growth factor receptor (EGFR) T790M-mutated non-small cell lung cancer (NSCLC) has been demonstrated in clinical trials, but real-world data, particularly regarding resistance profile, remains limited. This study aims to analyze the resistance mechanisms acquired after treatment with Osimertinib. Clinical outcomes and molecular results from re-biopsies at the time of osimertinib progression of EGFR T790M-mutated NSCLC patient were analyzed. Twenty-one patients with stage IV adenocarcinoma were included [median 69 years; 57.1% female; 85.7% never-smokers; 23.8% ECOG performance status (PS) ≥2]. Median PFS and OS were 13.4 (95% CI: 8.0–18.9) and 26.4 (95% IC: 8.9–43.8) months, respectively. At the time of analysis, 10 patients had tumor progression (47.6%). T790M loss occurred in 50%, being associated with earlier progression (median PFS 8.1 vs. 21.4 months, p = 0.011). Diverse molecular alterations were identified, including C797S mutation (n = 1), PIK3CA mutation (n = 2), MET amplification (n = 1), CTNNB1 mutation (n = 1), and DCTN1-ALK fusion (n = 1). Histological transformation into small cell carcinoma occurred in one patient. This real-world life study highlights the relevance of re-biopsy at the time of disease progression, contributing to understand resistance mechanisms and to guide treatment strategies.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFernandes, M. G. O., Sousa, C., Jacob, M., Almeida, L., Santos, V., Araújo, D., Novais Bastos, H., Magalhães, A., Cirnes, L., Moura, C. S., Queiroga, H., Cruz-Martins, N., & Hespanhol, V. (2021). Resistance Profile of Osimertinib in Pre-treated Patients With EGFR T790M-Mutated Non-small Cell Lung Cancer. Frontiers in Oncology, 11, 1–7. https://doi.org/doi.org/10.3389/fonc.2021.602924pt_PT
dc.identifier.doidoi.org/10.3389/fonc.2021.602924pt_PT
dc.identifier.eissn2234-943X
dc.identifier.urihttp://hdl.handle.net/10400.22/25058
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationPTDC/PSIGER/ 28076/2017pt_PT
dc.relation.publisherversionhttps://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.602924/fullpt_PT
dc.subjectNon-small cell lung cancerpt_PT
dc.subjectEGFR T790M mutationpt_PT
dc.subjectOsimertinibpt_PT
dc.subjectResistancept_PT
dc.subjectReal-world datapt_PT
dc.subjectNext generation sequencingpt_PT
dc.titleResistance profile of osimertinib in pre-treated patients with EGFR T790M-mutated non-small cell lung cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage7pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleFrontiers in Oncologypt_PT
oaire.citation.volume11pt_PT
person.familyNameCirnes
person.givenNameLuís
person.identifier.ciencia-idA412-0AC5-0780
person.identifier.orcid0000-0002-2348-5878
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication17b01de2-29be-4571-8edd-d7fb6154b26c
relation.isAuthorOfPublication.latestForDiscovery17b01de2-29be-4571-8edd-d7fb6154b26c

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