FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2978342398> ?p ?o ?g. }

• W2978342398 endingPage "v627" @default.
• W2978342398 startingPage "v627" @default.
• W2978342398 abstract "Abstract Background Osimertinib (osi) is a third-generation EGFR-TKI selective for sensitizing (EGFRm) and p.T790M resistance mutations approved for metastatic NSCLC. Despite a primary benefit, almost all patients (pts) develop acquired resistance, whose mechanisms are not completely characterized. Methods Metastatic NSCLC pts who performed a tissue and plasma biopsy at osi progression, and optionally before, were identified from the prospective MATCH-R trial (NCT02517892). Targeted next-generation sequencing (NGS, 74 to 82 genes), comparative genomic hybridization (CGH), whole exome sequencing (WES), and RNA sequencing (RNA-Seq) were performed on the tissue. All molecular alterations were reviewed, those related to definitive or potential resistance mechanism were included in the analysis. Results The 31 pts included (23 [74%] women) had the tissue biopsy analysis at osi progression by NGS (97%), CGH (87%) and WES+RNA-Seq (61%). Additional cfDNA genomic profile was available for 17 pts (55%). Two pts received osi as first-line and 29 (94%) at previous EGFR TKI resistance. Most frequent acquired resistance to osi was EGFR on-target alterations (n = 12, 39%): 9 p.C797S, 2 p.L817Q and 1 EGFR amplification (amp). 4 pts (3 p.C797S and 1 p.L817Q) also had EGFR amp as potential concurrent resistance. Off-target resistance alterations were found in 11 (35%) tumors: 5 fusions involving oncogenes (16%, RET, MET, BRAF, ALK, FGFR3, and NTRK1), 2 with BRAF p.V600E mutation (6%) which co-occurred with p.C797S, then MET amp, HER2 amp, KRAS mut, and PIK3CA mut in 1 (3%). More than one resistance mechanism was found in 14 tumors (45%), more than two in 5 (16%). DNA repair gene alterations were observed in 10 pts (32%). Median TMB, assessed in 18 tumors, was 2.52 mutations/Mb, 1 was classified as high. p.T790M loss (54%) was associated with a more aggressive progression pattern compared with p.T790M maintain. For 20 pts a paired pre-osi biopsy was analyzed; 4 alterations (20%, 1 on-target, 3 off-target) were already detected. Conclusions Resistance mechanisms to osi are more complex than expected since more than one alteration was recognized in 45% of pts. Combination strategy might be needed. Clinical trial identification NCT02517892. Legal entity responsible for the study The authors. Funding Diego Enrico was recipient of the grant DUERTECC (Diplome Universitaire Europeen de Recherche Translationnelle et Clinique en Cancerologie) for 2018-2019. Disclosure Y. Loriot: Honoraria (self): Roche, MSD, Astellas, Janssen, AstraZeneca, BMS, Seattle Genetics, Sanofi, Clovis, Pfizer; Honoraria (institution): Roche, MSD, Astellas, Janssen, AstraZeneca, BMS, Seattle Genetics, Sanofi, Clovis, Incyte, Pfizer; Research grant / Funding (institution): Roche, MSD, Sanofi; Travel / Accommodation / Expenses: Roche, MSD, Janssen, AstraZeneca, Seattle Genetics,; Licensing / Royalties: Pending patent (USA 62/455211, Europe 17209098.7). D. Planchard: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, AbbVie, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel / Accommodation / Expenses: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim , Roche, Merck,Novartis, prIME Oncology, Pfizer. S. Michiels: Advisory / Consultancy, Statistical advice : Janssen Cilag France; Advisory / Consultancy, Data and safety monitoring member : Hexal, JJ Research grant / Funding (institution): Astrazeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-remunerated activity/ies: Astrazeneca, Bayer, BMS, Boringher Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche; Advisory / Consultancy: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, Novartis, Pfizer, Roche, Sanofi, Orion . J. Soria: Advisory / Consultancy: AstraZeneca, BMS, Merck, Pfi zer/Merck Serono, and Roche; Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: AstraZeneca. F. Andre: Research grant / Funding (institution): NVS, AZ, Roche, Daiichi, Lilly, Pfizer. B. Besse: Research grant / Funding (institution): AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. All other authors have declared no conflicts of interest." @default.
• W2978342398 created "2019-10-10" @default.
• W2978342398 creator A5001814176 @default.
• W2978342398 creator A5003964504 @default.
• W2978342398 creator A5009379815 @default.
• W2978342398 creator A5009978511 @default.
• W2978342398 creator A5012092551 @default.
• W2978342398 creator A5021624793 @default.
• W2978342398 creator A5023794502 @default.
• W2978342398 creator A5025583232 @default.
• W2978342398 creator A5027991868 @default.
• W2978342398 creator A5028596081 @default.
• W2978342398 creator A5039491281 @default.
• W2978342398 creator A5042575799 @default.
• W2978342398 creator A5046169054 @default.
• W2978342398 creator A5057151895 @default.
• W2978342398 creator A5065209996 @default.
• W2978342398 creator A5067202962 @default.
• W2978342398 creator A5070791805 @default.
• W2978342398 creator A5075283807 @default.
• W2978342398 creator A5090082356 @default.
• W2978342398 creator A5090177578 @default.
• W2978342398 date "2019-10-01" @default.
• W2978342398 modified "2023-10-17" @default.
• W2978342398 title "Multiple synchronous mechanisms may contribute to osimertinib resistance in non-small cell lung cancer (NSCLC) patients: Insights of the MATCH-R study" @default.
• W2978342398 doi "https://doi.org/10.1093/annonc/mdz260.048" @default.
• W2978342398 hasPublicationYear "2019" @default.
• W2978342398 type Work @default.
• W2978342398 sameAs 2978342398 @default.
• W2978342398 citedByCount "2" @default.
• W2978342398 countsByYear W29783423982022 @default.
• W2978342398 countsByYear W29783423982023 @default.
• W2978342398 crossrefType "journal-article" @default.
• W2978342398 hasAuthorship W2978342398A5001814176 @default.
• W2978342398 hasAuthorship W2978342398A5003964504 @default.
• W2978342398 hasAuthorship W2978342398A5009379815 @default.
• W2978342398 hasAuthorship W2978342398A5009978511 @default.
• W2978342398 hasAuthorship W2978342398A5012092551 @default.
• W2978342398 hasAuthorship W2978342398A5021624793 @default.
• W2978342398 hasAuthorship W2978342398A5023794502 @default.
• W2978342398 hasAuthorship W2978342398A5025583232 @default.
• W2978342398 hasAuthorship W2978342398A5027991868 @default.
• W2978342398 hasAuthorship W2978342398A5028596081 @default.
• W2978342398 hasAuthorship W2978342398A5039491281 @default.
• W2978342398 hasAuthorship W2978342398A5042575799 @default.
• W2978342398 hasAuthorship W2978342398A5046169054 @default.
• W2978342398 hasAuthorship W2978342398A5057151895 @default.
• W2978342398 hasAuthorship W2978342398A5065209996 @default.
• W2978342398 hasAuthorship W2978342398A5067202962 @default.
• W2978342398 hasAuthorship W2978342398A5070791805 @default.
• W2978342398 hasAuthorship W2978342398A5075283807 @default.
• W2978342398 hasAuthorship W2978342398A5090082356 @default.
• W2978342398 hasAuthorship W2978342398A5090177578 @default.
• W2978342398 hasBestOaLocation W29783423981 @default.
• W2978342398 hasConcept C121608353 @default.
• W2978342398 hasConcept C126322002 @default.
• W2978342398 hasConcept C143998085 @default.
• W2978342398 hasConcept C2775999482 @default.
• W2978342398 hasConcept C2776256026 @default.
• W2978342398 hasConcept C2777626846 @default.
• W2978342398 hasConcept C2779177807 @default.
• W2978342398 hasConcept C2781182431 @default.
• W2978342398 hasConcept C502942594 @default.
• W2978342398 hasConcept C71924100 @default.
• W2978342398 hasConcept C81729549 @default.
• W2978342398 hasConceptScore W2978342398C121608353 @default.
• W2978342398 hasConceptScore W2978342398C126322002 @default.
• W2978342398 hasConceptScore W2978342398C143998085 @default.
• W2978342398 hasConceptScore W2978342398C2775999482 @default.
• W2978342398 hasConceptScore W2978342398C2776256026 @default.
• W2978342398 hasConceptScore W2978342398C2777626846 @default.
• W2978342398 hasConceptScore W2978342398C2779177807 @default.
• W2978342398 hasConceptScore W2978342398C2781182431 @default.
• W2978342398 hasConceptScore W2978342398C502942594 @default.
• W2978342398 hasConceptScore W2978342398C71924100 @default.
• W2978342398 hasConceptScore W2978342398C81729549 @default.
• W2978342398 hasLocation W29783423981 @default.
• W2978342398 hasOpenAccess W2978342398 @default.
• W2978342398 hasPrimaryLocation W29783423981 @default.
• W2978342398 hasRelatedWork W2079526095 @default.
• W2978342398 hasRelatedWork W2390152934 @default.
• W2978342398 hasRelatedWork W2569956255 @default.
• W2978342398 hasRelatedWork W2982085891 @default.
• W2978342398 hasRelatedWork W3039972379 @default.
• W2978342398 hasRelatedWork W3095217392 @default.
• W2978342398 hasRelatedWork W3134043497 @default.
• W2978342398 hasRelatedWork W4200084736 @default.
• W2978342398 hasRelatedWork W4308323206 @default.
• W2978342398 hasRelatedWork W4318323499 @default.
• W2978342398 hasVolume "30" @default.
• W2978342398 isParatext "false" @default.
• W2978342398 isRetracted "false" @default.
• W2978342398 magId "2978342398" @default.
• W2978342398 workType "article" @default.