TY - JOUR
T1 - RET-MAP
T2 - An International Multicenter Study on Clinicobiologic Features and Treatment Response in Patients With Lung Cancer Harboring a RET Fusion
AU - Aldea, Mihaela
AU - Marinello, Arianna
AU - Duruisseaux, Michael
AU - Zrafi, Wael
AU - Conci, Nicole
AU - Massa, Giacomo
AU - Metro, Giulio
AU - Monnet, Isabelle
AU - Gomez Iranzo, Patricia
AU - Tabbo, Fabrizio
AU - Bria, Emilio
AU - Guisier, Florian
AU - Vasseur, Damien
AU - Lindsay, Colin R.
AU - Ponce-Aix, Santiago
AU - Cousin, Sophie
AU - Citarella, Fabrizio
AU - Fallet, Vincent
AU - Minatta, Jose Nicolas
AU - Eisert, Anna
AU - de Saint Basile, Hortense
AU - Audigier-Valette, Clarisse
AU - Mezquita, Laura
AU - Calles, Antonio
AU - Mountzios, Giannis
AU - Tagliamento, Marco
AU - Remon Masip, Jordi
AU - Raimbourg, Judith
AU - Terrisse, Safae
AU - Russo, Alessandro
AU - Cortinovis, Diego
AU - Rochigneux, Philippe
AU - Pinato, David James
AU - Cortellini, Alessio
AU - Leonce, Camille
AU - Gazzah, Anas
AU - Ghigna, Maria Rosa
AU - Ferrara, Roberto
AU - Dall'Olio, Filippo Gustavo
AU - Passiglia, Francesco
AU - Ludovini, Vienna
AU - Barlesi, Fabrice
AU - Felip, Enriqueta
AU - Planchard, David
AU - Besse, Benjamin
N1 - Publisher Copyright:
© 2023 International Association for the Study of Lung Cancer
PY - 2023/5/1
Y1 - 2023/5/1
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Immunotherapy
KW - Non–small cell lung cancer
KW - RET fusion
KW - RET inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85149658996&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2022.12.018
DO - 10.1016/j.jtho.2022.12.018
M3 - Article
C2 - 36646211
AN - SCOPUS:85149658996
SN - 1556-0864
VL - 18
SP - 576
EP - 586
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 5
ER -