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

Autor: 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 Eisert, Hortense 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
Přispěvatelé: 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
Rok vydání: 2023
Předmět:
Pulmonary and Respiratory Medicine
Otros calificadores::Otros calificadores::/genética [Otros calificadores]
RET inhibitors
Pulmons - Càncer - Aspectes genètics
Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma
Bronchogenic::Carcinoma
Non-Small-Cell Lung [DISEASES]
neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES]
chemotherapy
RET fusion
immunotherapy
non-small cell lung cancer
Anomalies cromosòmiques
Oncology
Other subheadings::Other subheadings::/genetics [Other subheadings]
aminoácidos
péptidos y proteínas::proteínas::proteínas mutantes::proteínas mutantes quiméricas::proteínas oncogénicas de fusión [COMPUESTOS QUÍMICOS Y DROGAS]
Amino Acids
Peptides
and Proteins::Proteins::Mutant Proteins::Mutant Chimeric Proteins::Oncogene Proteins
Fusion [CHEMICALS AND DRUGS]
Zdroj: Scientia
ISSN: 1556-0864
DOI: 10.1016/j.jtho.2022.12.018
Popis: Chemotherapy; Non–small cell lung cancer; RET inhibitors Quimioteràpia; Càncer de pulmó de cèl·lules no petites; Inhibidors de RET Quimioterapia; Cáncer de pulmón de células no pequeñas; Inhibidores de RET 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. Writing assistance was provided by Mrs. Sarah Mackenzie. Dr. Marinello was the recipient for the grant for DUERTECC/EURONCO (Diplôme Universitaire Européen de Recherche Translationnelle Et Clinique en Cancérologie). Dr. Mezquita received support from the Contrato Juan Rodes 2020 (ISCIII, Ministry of Health); Ayuda de la Acción Estratégica en Salud-ISCIII FIS 2021 (PI21/01653); Ayuda SEOM-Juan Rodés 2020. Dr. Cortellini acknowledges the support from the National Institute for Health Research Imperial Biomedical Research Centre. Dr. Pinato acknowledges the support from the Wellcome Trust Strategic Fund (PS3416), Associazione Italiana per la Ricerca sul Cancro (Associazione Italiana per la Ricerca sul Cancro MFAG Grant ID 25697), National Institute for Health Research Imperial Biomedical Research Centre, Imperial Experimental Cancer Medicine Centre, and the Imperial College Tissue Bank.
Databáze: OpenAIRE
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