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dc.contributor.authorMazieres, J
dc.contributor.authorDrilon, A
dc.contributor.authorLusque, A
dc.contributor.authorMhanna, L
dc.contributor.authorCortot, AB
dc.contributor.authorMezquita, L
dc.contributor.authorThai, AA
dc.contributor.authorMascaux, C
dc.contributor.authorCouraud, S
dc.contributor.authorVeillon, R
dc.contributor.authorVan den Heuvel, M
dc.contributor.authorNeal, J
dc.contributor.authorPeled, N
dc.contributor.authorFrüh, M
dc.contributor.authorNg, TL
dc.contributor.authorGounant, V
dc.contributor.authorPopat, S
dc.contributor.authorDiebold, J
dc.contributor.authorSabari, J
dc.contributor.authorZhu, VW
dc.contributor.authorRothschild, SI
dc.contributor.authorBironzo, P
dc.contributor.authorMartinez-Marti, A
dc.contributor.authorCurioni-Fontecedro, A
dc.contributor.authorRosell, R
dc.contributor.authorLattuca-Truc, M
dc.contributor.authorWiesweg, M
dc.contributor.authorBesse, B
dc.contributor.authorSolomon, B
dc.contributor.authorBarlesi, F
dc.contributor.authorSchouten, RD
dc.contributor.authorWakelee, H
dc.contributor.authorCamidge, DR
dc.contributor.authorZalcman, G
dc.contributor.authorNovello, S
dc.contributor.authorOu, SI
dc.contributor.authorMilia, J
dc.contributor.authorGautschi, O
dc.date.accessioned2019-09-18T13:46:45Z
dc.date.issued2019-08
dc.identifier.citationAnnals of oncology : official journal of the European Society for Medical Oncology, 2019, 30 (8), pp. 1321 - 1328
dc.identifier.issn0923-7534
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3347
dc.identifier.eissn1569-8041
dc.identifier.doi10.1093/annonc/mdz167
dc.description.abstractBackground Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.Patients and methods We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.Results We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).Conclusions : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.
dc.formatPrint
dc.format.extent1321 - 1328
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectHumans
dc.subjectCarcinoma, Non-Small-Cell Lung
dc.subjectLung Neoplasms
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectRegistries
dc.subjectRetrospective Studies
dc.subjectMutation
dc.subjectOncogenes
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectProgrammed Cell Death 1 Receptor
dc.subjectResponse Evaluation Criteria in Solid Tumors
dc.subjectBiomarkers, Tumor
dc.subjectAntineoplastic Agents, Immunological
dc.subjectB7-H1 Antigen
dc.subjectProgression-Free Survival
dc.titleImmune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/annonc/mdz167
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2019-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAnnals of oncology : official journal of the European Society for Medical Oncology
pubs.issue8
pubs.notesNot known
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.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
pubs.volume30
pubs.embargo.termsNot known
icr.researchteamThoracic Oncologyen_US
dc.contributor.icrauthorPopat, Sanjayen


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