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