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Article Dans Une Revue Journal of Thoracic Oncology Année : 2023

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

1 IGR - Institut Gustave Roussy
2 Université Paris-Saclay
3 Humanitas Cancer Center [Milano, Italy]
4 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
5 Hôpital Louis Pradel [CHU - HCL]
6 AOUB - IRCCS Azienda Ospedaliero-Universitaria di Bologna
7 Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan]
8 Ospedale "Santa Maria della Misericordia" = University Hospital "Santa Maria della Misericordia"
9 Service de Pneumologie [CHI Créteil]
10 Vall d'Hebron University Hospital [Barcelona]
11 UNITO - Università degli studi di Torino = University of Turin
12 San Luigi Hospital [Turin, Italy]
13 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
14 Unicatt - Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma]
15 CHU Rouen
16 The Christie NHS Foundation Trust [Manchester, Royaume-Uni]
17 University Hospital October 12
18 Institut Bergonié [Bordeaux]
19 UCBM - Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome
20 CHU Tenon [AP-HP]
21 Hospital Italiano de Buenos Aires
22 University Hospital of Cologne [Cologne]
23 HEGP - Hôpital Européen Georges Pompidou [APHP]
24 Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse
25 Clinic Barcelona Hospital Universitari
26 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
27 Hospital General Universitario "Gregorio Marañón" [Madrid]
28 Henry Dunant Hospital [Athens, Greece]
29 UniGe - Università degli studi di Genova = University of Genoa
30 Centro Integral Oncologico Clara Campal
31 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
32 AP-HP - Hopital Saint-Louis [AP-HP]
33 SGH - San Gerardo Hospital [Monza, Italy]
34 IPC - Institut Paoli-Calmettes
35 Imperial College London
36 Università del Piemonte Orientale - Dipartimento DISIT Italy
Florian Guisier
  • Fonction : Auteur
Vincent Fallet
  • Fonction : Auteur
Alessandro Russo
  • Fonction : Auteur

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.
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hal-04519993 , version 1 (03-06-2024)

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Mihaela Aldea, Arianna Marinello, Michael Duruisseaux, Wael Zrafi, Nicole Conci, et al.. RET-MAP: An International Multicenter Study on Clinicobiologic Features and Treatment Response in Patients With Lung Cancer Harboring a RET Fusion. Journal of Thoracic Oncology, 2023, 18 (5), pp.576-586. ⟨10.1016/j.jtho.2022.12.018⟩. ⟨hal-04519993⟩
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