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dc.contributor.authorYang, JC-H
dc.contributor.authorSchuler, M
dc.contributor.authorPopat, S
dc.contributor.authorMiura, S
dc.contributor.authorPark, K
dc.contributor.authorPassaro, A
dc.contributor.authorDe Marinis, F
dc.contributor.authorSolca, F
dc.contributor.authorMärten, A
dc.contributor.authorKim, ES
dc.coverage.spatialSwitzerland
dc.date.accessioned2022-07-12T14:41:21Z
dc.date.available2022-07-12T14:41:21Z
dc.date.issued2022-04-28
dc.identifierARTN 834704
dc.identifier.citationFrontiers in Oncology, 2022, 12 pp. 834704 -en_US
dc.identifier.issn2234-943X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5208
dc.identifier.eissn2234-943X
dc.identifier.eissn2234-943X
dc.identifier.doi10.3389/fonc.2022.834704
dc.identifier.doi10.3389/fonc.2022.834704
dc.description.abstractIntroduction: Previously, we developed a database of 693 patients with NSCLC and uncommon EGFR mutations treated with afatinib. Here, we provide an update of >1000 patients, with more data on specific mutations. Methods: Patients were identified from a prospective database developed by Boehringer Ingelheim and via literature review. Mutations were categorized as T790M-positive, exon 20 insertions, major uncommon (G719X, L861Q, S768I) and 'others'. Patients with compound mutations (≥2 EGFR mutations) were analyzed separately. Key endpoints were time to treatment failure (TTF) and objective response rate (ORR). Results: Of 1023 patients included, 587 patients were EGFR TKI-naïve and 425 were EGFR TKI-pretreated. The distribution of mutation categories was: major uncommon (41.4%); exon 20 insertions (22.3%); T790M (20.3%); and 'others' (15.9%); 38.6% had compound mutations. Overall, median TTF (TKI naïve/pretreated) was 10.7 and 4.5 months. ORR was 49.8% and 26.8%, respectively. In TKI-naïve patients, afatinib demonstrated activity against major uncommon mutations (median TTF: 12.6 months; ORR: 59.0%), 'other' mutations (median TTF: 10.7 months; ORR: 63.9%) including strong activity against E709X (11.4 months; 84.6%) and L747X (14.7 months; 80.0%), and compound mutations (11.5 months; 63.9%). Although sample sizes were small, notable activity was observed against specific exon 20 insertions at residues A763, M766, N771, and V769, and against osimertinib resistance mutations (G724S, L718X, C797S). Conclusion: Afatinib should be considered as a first-line treatment option for NSCLC patients with major uncommon, compound, 'other' (including E709X and L747X) and some specific exon 20 insertion mutations. Moderate activity was seen against osimertinib resistance EGFR mutations.
dc.formatElectronic-eCollection
dc.format.extent834704 -
dc.languageeng
dc.language.isoengen_US
dc.publisherFRONTIERS MEDIA SAen_US
dc.relation.ispartofFrontiers in Oncology
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectEGFR exon 20 insertions
dc.subjectafatinib
dc.subjectcompound mutations
dc.subjectnon-small-cell lung cancer
dc.subjectuncommon EGFR mutations
dc.titleAfatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: An Updated Database of 1023 Cases Brief Report.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-02-23
dc.date.updated2022-07-12T14:40:38Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.3389/fonc.2022.834704en_US
rioxxterms.licenseref.startdate2022-04-28
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35574304
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Thoracic Oncology/Thoracic Oncology (hon.)
pubs.publication-statusPublished online
pubs.volume12
dc.contributor.icrauthorPopat, Sanjay
icr.provenanceDeposited by Mr Arek Surman on 2022-07-12. Deposit type is initial. No. of files: 1. Files: Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon iEGFRi Mutations An Updated Database of 1023 Cas.pdf


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