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

Mihaela Aldea, Arianna Marinello, Michael Duruisseaux, Wael Zrafi, Nicole Conci, Giacomo Massa, Giulio Metro, Isabelle Monnet, Patricia Gomez Iranzo, Fabrizio Tabbo, Emilio Bria, Florian Guisier, Damien Vasseur, Colin R. Lindsay, Santiago Ponce-Aix, Sophie Cousin, Fabrizio Citarella, Vincent Fallet, Jose Nicolas Minatta, Anna EisertHortense de Saint Basile, Clarisse Audigier-Valette, Laura Mezquita, Antonio Calles, Giannis Mountzios, Marco Tagliamento, Jordi Remon Masip, Judith Raimbourg, Safae Terrisse, Alessandro Russo, Diego Cortinovis, Philippe Rochigneux, David James Pinato, Alessio Cortellini, Camille Leonce, Anas Gazzah, Maria Rosa Ghigna, Roberto Ferrara, Filippo Gustavo Dall'Olio, Francesco Passiglia, Vienna Ludovini, Fabrice Barlesi, Enriqueta Felip, David Planchard, Benjamin Besse

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    23 Citations (Scopus)

    Résumé

    Introduction: Nearly 1% to 2% of NSCLCs harbor RET fusions. Characterization of this rare population is still incomplete. Methods: 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. Results: 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). Conclusions: 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.

    langue originaleAnglais
    Pages (de - à)576-586
    Nombre de pages11
    journalJournal of Thoracic Oncology
    Volume18
    Numéro de publication5
    Les DOIs
    étatPublié - 1 mai 2023

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