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  • Drilon, AlexanderMem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.;Weill Cornell Med Coll, New York, NY USA. (author)

Clinicopathologic Features and Response to Therapy of NRG1 Fusion-Driven Lung Cancers : The eNRGy1 Global Multicenter Registry

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • LIPPINCOTT WILLIAMS & WILKINS,2021
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-458408
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-458408URI
  • https://doi.org/10.1200/JCO.20.03307DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:147897013URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • PURPOSE Although NRG1 fusions are oncogenic drivers across multiple tumor types including lung cancers, these are difficult to study because of their rarity. The global eNRGy1 registry was thus established to characterize NRG1 fusion-positive lung cancers in the largest and most diverse series to date. METHODS From June 2018 to February 2020, a consortium of 22 centers from nine countries in Europe, Asia, and the United States contributed data from patients with pathologically confirmed NRG1 fusion-positive lung cancers. Profiling included DNA-based and/or RNA-based next-generation sequencing and fluorescence in situ hybridization. Anonymized clinical, pathologic, molecular, and response (RECIST v1.1) data were centrally curated and analyzed. RESULTS Although the typified never smoking (57%), mucinous adenocarcinoma (57%), and nonmetastatic (71%) phenotype predominated in 110 patients with NRG1 fusion-positive lung cancer, further diversity, including in smoking history (43%) and histology (43% nonmucinous and 6% nonadenocarcinoma), was elucidated. RNA-based testing identified most fusions (74%). Molecularly, six (of 18) novel 5 ' partners, 20 unique epidermal growth factor domain-inclusive chimeric events, and heterogeneous 5 '/3 ' breakpoints were found. Platinum-doublet and taxane-based (post-platinum-doublet) chemotherapy achieved low objective response rates (ORRs 13% and 14%, respectively) and modest progression-free survival medians (PFS 5.8 and 4.0 months, respectively). Consistent with a low programmed death ligand-1 expressing (28%) and low tumor mutational burden (median: 0.9 mutations/megabase) immunophenotype, the activity of chemoimmunotherapy and single-agent immunotherapy was poor (ORR 0%/PFS 3.3 months and ORR 20%/PFS 3.6 months, respectively). Afatinib achieved an ORR of 25%, not contingent on fusion type, and a 2.8-month median PFS. CONCLUSION NRG1 fusion-positive lung cancers were molecularly, pathologically, and clinically more heterogeneous than previously recognized. The activity of cytotoxic, immune, and targeted therapies was disappointing. Further research examining NRG1-rearranged tumor biology is needed to develop new therapeutic strategies.

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  • Duruisseaux, MichaelHosp Civils Lyon, Louis Pradel Hosp, Resp Dept, Canc Inst, Lyon, France.;Canc Res Ctr Lyon, Anticanc Antibodies Lab, Lyon, France.;Univ Lyon, Univ Claude Bernard Lyon, UMR INSERM 1052 CNRS 528, Lyon, France. (author)
  • Han, Ji-YounNatl Canc Ctr, Goyang Si, South Korea. (author)
  • Ito, MasaokiQuiron Dexeus Univ Inst, Pangaea Oncol, Barcelona, Spain.;Inst Hlth Sci Res Germans Trias & Pujol IGTP, Badalona, Spain.;Hiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima, Japan. (author)
  • Falcon, ChristinaMem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.;Weill Cornell Med Coll, New York, NY USA. (author)
  • Yang, Soo-RyumMem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.;Weill Cornell Med Coll, New York, NY USA. (author)
  • Murciano-Goroff, Yonina R.Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. (author)
  • Chen, HaiquanFudan Univ, Shanghai Canc Ctr, Shanghai Med Coll, Shanghai, Peoples R China.;Fudan Univ, Sch Life Sci, Inst Thorac Oncol, State Key Lab Genet Engn, Shanghai, Peoples R China. (author)
  • Okada, MorihitoHiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima, Japan. (author)
  • Molina, Miguel AngelQuiron Dexeus Univ Inst, Lab Mol Biol, Pangaea Oncol, Barcelona, Spain. (author)
  • Wislez, MarieSorbonne Univ, INSERM, Ctr Rech Cordeliers, Univ Paris, Paris, France.;Hop Cochin, AP HP, Pulmonol Dept, Team Inflammat Complement & Canc, Paris, France.;Hop Cochin, AP HP, Pulmonol Dept, Oncol Thorac Unit, Paris, France. (author)
  • Brun, PhilippeHelios Klinikum Emil von Behring, Lungenklin Heckeshorn, Dept Pneumol, Valence, France. (author)
  • Dupont, ClarisseHosp Civils Lyon, Louis Pradel Hosp, Resp Dept, Canc Inst, Lyon, France. (author)
  • Brandén, EvaUppsala universitet,Centrum för klinisk forskning, Gävleborg,Karolinska Inst, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden.(Swepub:uu)evabr789 (author)
  • Rossi, GiulioInfermi Hosp, Local Hlth Author Romagna, Rimini, Italy.;St Maria delle Croci Hosp, Local Hlth Author Romagna, Ravenna, Italy. (author)
  • Schrock, AlexaFdn Med Inc, Cambridge, MA USA. (author)
  • Ali, SirajFdn Med Inc, Cambridge, MA USA. (author)
  • Gounant, ValerieHop Tenon, Assistance Publ Hop Paris, Dept Pulmonol, Paris, France. (author)
  • Magne, FannyHop Nord Ouest Villefranche Sur Saone, Gleize, France. (author)
  • Blum, Torsten GerrietKlinikum Emil von Behring, Dept Pneumol, Berlin, Germany. (author)
  • Schram, Alison M.Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. (author)
  • Monnet, IsabelleCtr Hosp Intercommunal Creteil, Creteil, France. (author)
  • Shih, Jin-YuanNatl Taiwan Univ, Natl Taiwan Univ Hosp, Taipei, Taiwan.;Natl Taiwan Univ, Coll Med, Taipei, Taiwan. (author)
  • Sabari, JoshuaNew York Univ Langone Hlth, Perlmutter Canc Ctr, New York, NY USA. (author)
  • Perol, MauriceLeon Berard Canc Ctr, Lyon, France. (author)
  • Zhu, Viola W.Univ Calif Irvine, Irvine Sch Med, Dept Med, Div Hematol Oncol,Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. (author)
  • Nagasaka, MisakoWayne State Univ, Karmanos Canc Inst, Detroit, MI USA.;St Marianna Univ, Dept Internal Med, Div Neurol, Kawasaki, Kanagawa, Japan. (author)
  • Doebele, RobertUniv Colorado, Div Med Oncol, Canc Ctr, Aurora, CO USA. (author)
  • Camidge, D. RossUniv Colorado, Div Med Oncol, Canc Ctr, Aurora, CO USA. (author)
  • Arcila, MariaMem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.;Weill Cornell Med Coll, New York, NY USA. (author)
  • Ou, Sai-Hong IgnatiusUniv Calif Irvine, Irvine Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. (author)
  • Moro-Sibilot, DenisCtr Hosp Univ Grenoble, Pole Med Aigue Communautaire, Clin Pneumol, Grenoble, France. (author)
  • Rosell, RafaelHosp Badalona Germans Trias & Pujol, Catalan Inst Oncol, Badalona, Spain. (author)
  • Muscarella, Lucia AnnaFdn IRCCS Casa Sollievo della Sofferenza, Lab Oncol, Foggia, Italy. (author)
  • Liu, Stephen, VGeorgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. (author)
  • Cadranel, JacquesSorbonne Univ, Tenon Hosp, Assistance Publ Hop Paris, Dept Pneumol & Thorac Oncol, Paris, France.;Sorbonne Univ, GRC Theranoscan, Paris, France. (author)
  • Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.;Weill Cornell Med Coll, New York, NY USA.Hosp Civils Lyon, Louis Pradel Hosp, Resp Dept, Canc Inst, Lyon, France.;Canc Res Ctr Lyon, Anticanc Antibodies Lab, Lyon, France.;Univ Lyon, Univ Claude Bernard Lyon, UMR INSERM 1052 CNRS 528, Lyon, France. (creator_code:org_t)

Related titles

  • In:Journal of Clinical Oncology: LIPPINCOTT WILLIAMS & WILKINS39:25, s. 2791-28020732-183X1527-7755

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