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RET-MAP: An International Multicenter Study on Clinicobiologic Features and Treatment Response in Patients With Lung Cancer Harboring a RET Fusion

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  • Additional Information
    • Contributors:
      Catois, Jacques-Olivier; Institut Català de la Salut; [Aldea M] Department of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, France. Paris-Saclay University, Kremlin-Bicêtre, France. [Marinello A] Department of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, France. Department of Medical Oncology, Humanitas Research Hospital, Milan, Italy. [Duruisseaux M] Respiratory Department and Early Phase, Louis Pradel Hospital, Hospices Civils de Lyon. Cancer Research Center of Lyon (CRCL). Univ Lyon, Lyon, France. [Zrafi W] Department of Biostatistics and Bioinformatics, Gustave Roussy, Villejuif, France. [Conci N] Department of Medical Oncology, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) University Hospital of Bologna, Bologna, Italy. [Massa G] Department of Medical Oncology, National Cancer Institut, Milan, Italy. [Gomez Iranzo P, Felip E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain; Vall d'Hebron Barcelona Hospital Campus; Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS); Laboratoire d'Informatique, du Traitement de l'Information et des Systèmes (LITIS); Université Le Havre Normandie (ULH); Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN); Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie); Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH); Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA); Aldea, M.; Marinello, A.; Duruisseaux, M.; Zrafi, W.; Conci, N.; Massa, G.; Metro, G.; Monnet, I.; Gomez Iranzo, P.; Tabbo, F.; Bria, E.; Guisier, F.; Vasseur, D.; Lindsay, C. R.; Ponce-Aix, S.; Cousin, S.; Citarella, F.; Fallet, V.; Minatta, J. N.; Eisert, A.; de Saint Basile, H.; Audigier-Valette, C.; Mezquita, L.; Calles, A.; Mountzios, G.; Tagliamento, M.; Remon Masip, J.; Raimbourg, J.; Terrisse, S.; Russo, A.; Cortinovis, D.; Rochigneux, P.; Pinato, D. J.; Cortellini, A.; Leonce, C.; Gazzah, A.; Ghigna, M. -R.; Ferrara, R.; Dall'Olio, F. G.; Passiglia, F.; Ludovini, V.; Barlesi, F.; Felip, E.; Planchard, D.; Besse, B.
    • Publication Information:
      Elsevier BV, 2023.
    • Publication Date:
      2023
    • Abstract:
      Nearly 1% to 2% of NSCLCs harbor RET fusions. Characterization of this rare population is still incomplete.This retrospective multicenter study included patients with any-stage RET positive (RET+) NSCLC from 31 cancer centers. Molecular profiling included DNA/RNA sequencing or fluorescence in situ hybridization analyses. Clinicobiological features and treatment outcomes (per investigator) with surgery, chemotherapy (CT), immune checkpoint blockers (ICBs), CT-ICB, multityrosine kinase inhibitors, and RET inhibitors (RETis) were evaluated.For 218 patients included between February 2012 and April 2022, median age was 63 years, 56% were females, 93% had adenocarcinoma, and 41% were smokers. The most frequent fusion partner was KIF5B (72%). Median tumor mutational burden was 2.5 (range: 1-4) mutations per megabase, and median programmed death-ligand 1 expression was 10% (range: 0%-55%). The most common metastatic sites were the lung (50%), bone (43%), and pleura (40%). Central nervous system metastases were found at diagnosis of advanced NSCLC in 21% of the patients and at last follow-up or death in 31%. Overall response rate and median progression-free survival were 55% and 8.7 months with platinum doublet, 26% and 3.6 months with single-agent CT, 46% and 9.6 months with CT-ICB, 23% and 3.1 months with ICB, 37% and 3 months with multityrosine kinase inhibitor, and 76% and 16.2 months with RETi, respectively. Median overall survival was longer in patients treated with RETi versus no RETi (50.6 mo [37.7-72.1] versus 16.3 mo [12.7-28.8], p < 0.0001).Patients with RET+ NSCLC have mainly thoracic and bone disease and low tumor mutational burden and programmed death-ligand 1 expression. RETi markedly improved survival, whereas ICB may be active in selected patients.
    • File Description:
      application/pdf
    • ISSN:
      1556-0864
    • Accession Number:
      10.1016/j.jtho.2022.12.018
    • Rights:
      CC BY NC ND
    • Accession Number:
      edsair.doi.dedup.....57f7bd4756ed222514ab170ab21d1c3d