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

• Published in: Journal of thoracic oncology Vol. 18; no. 5; pp. 576 - 586
• Main Authors: 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, 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
• Format: Journal Article
• Language: English
• Published: Lippincott, Williams & Wilkins 01.05.2023
• Subjects: Cancer; Human health and pathology; Immunology; Immunotherapy; Life Sciences; Pharmaceutical sciences; Pharmacology; Pulmonology and respiratory tract; Santé publique et épidémiologie; Non–small cell lung cancer; Chemotherapy; RET fusion; Immunotherapy; RET inhibitors
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2022.12.018

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.