RET-MAP: An international multi-center study on clinicobiologic features and treatment response in patients with lung cancer harboring a RET fusion
Aldea, M. Marinello, A. Duruisseaux, M. Zrafi, W. Conci, N. Massa, G. Metro, G. Monnet, I. Gomez, P. I. Tabbo, F.
Aldea, M.
Marinello, A.
Duruisseaux, M.
Zrafi, W.
Conci, N.
Massa, G.
Metro, G.
Monnet, I.
Gomez, P. I.
Tabbo, F.
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Abstract
Introduction: Nearly 1-2% of non-small cell lung cancers (NSCLC) harbor RET fusions. Characterization of this rare population is still incomplete.
Methods: This retrospective multi-center study included patients with any-stage RET+ NSCLC from 31 cancer centers. Molecular profiling included DNA/RNA sequencing and/or FISH analyses. Clinico-biological features and treatment outcomes (per investigator) with surgery, chemotherapy, immune-checkpoint blockers (ICB), chemotherapy-ICB, multi-tyrosine kinase inhibitors (MTKi) and RET inhibitors (RETi) 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 (TMB) was 2.5 [range, 1-4] mut/Mb and median PD-L1 expression was 10% [range, 0-55]. The most common metastatic sites were lung (50%), bone (43%) and pleura (40%). Central nervous system metastases were found at diagnosis of advanced NSCLC in 21% of 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 chemotherapy, 46% and 9.6 months with chemotherapy-ICB, 23% and 3.1 months with ICB, 37% and 3 months with MTKi, and 76% and 16.2 months with RETi, respectively. Median overall survival was longer in patients treated with RETi versus no RETi (50.6 months [37.7-72.1] versus 16.3 months [12.7-28.8], P<0.0001).
Conclusions: Patients with RET+ NSCLC have mainly thoracic and bone disease, and low TMB and PD-L1 expression. RETi significantly improve survival, while ICB may be active in selected patients.
Authors
Aldea, M.
Marinello, A.
Duruisseaux, M.
Zrafi, W.
Conci, N.
Massa, G.
Metro, G.
Monnet, I.
Gomez, P. I.
Tabbo, F.
Bria, E.
Guisier, F.
Vasseur, D.
Lindsay, Colin R
Ponce, S.
Cousin, S.
Citarella, F.
Fallet, V.
Minatta, J. N.
Eisert, A.
de Saint Basile, H.
Audigier-Valette, C.
Mezquita, L.
Calles, A.
Mountzios, G.
Tagliamento, M.
Masip, J. R.
Raimbourg, J.
Terrisse, S.
Russo, A.
Cortinovis, D.
Rochigneux, P.
Pinato, D. J.
Cortellini, A.
Leonce, C.
Gazzah, A.
Ghigna, M. R.
Ferrara, R.
Dall'Olio, F. G.
Passiglia, F.
Ludovini, V.
Barlesi, F.
Felip, E.
Planchard, D.
Besse, B.
Marinello, A.
Duruisseaux, M.
Zrafi, W.
Conci, N.
Massa, G.
Metro, G.
Monnet, I.
Gomez, P. I.
Tabbo, F.
Bria, E.
Guisier, F.
Vasseur, D.
Lindsay, Colin R
Ponce, S.
Cousin, S.
Citarella, F.
Fallet, V.
Minatta, J. N.
Eisert, A.
de Saint Basile, H.
Audigier-Valette, C.
Mezquita, L.
Calles, A.
Mountzios, G.
Tagliamento, M.
Masip, J. R.
Raimbourg, J.
Terrisse, S.
Russo, A.
Cortinovis, D.
Rochigneux, P.
Pinato, D. J.
Cortellini, A.
Leonce, C.
Gazzah, A.
Ghigna, M. R.
Ferrara, R.
Dall'Olio, F. G.
Passiglia, F.
Ludovini, V.
Barlesi, F.
Felip, E.
Planchard, D.
Besse, B.
Description
Date
2023
Publisher
Collections
Keywords
Type
Article
Citation
Aldea M, Marinello A, Duruisseaux M, Zrafi W, Conci N, Massa G, et al. RET-MAP: An international multi-center study on clinicobiologic features and treatment response in patients with lung cancer harboring a RET fusion. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2023 Jan 13. PubMed PMID: 36646211. Epub 2023/01/17. eng.