Abstract 4019: RET-MAP: An international multi-center study of patients with advanced non-small cell lung cancer and RET fusions
Authors: Aldea Mihaela , Marinello Arianna , Zrafi Wael , Tabbo Fabrizio , Guisier Florian , Vasseur Damien , Fallet Vincent , Audigier-Valette Clarisse , Mezquita Laura , Calles Antonio , Mountzios Giannis , Tagliamento Marco , Raimbourg Judith , Terrisse Safae , Novello Silvia , Ghigna Maria-Rosa , Barlesi Fabrice , Planchard David , Besse Benjamin 
Published: June 2022

Abstract
Introduction: RET fusions (RET+) are identified in nearly 1% of advanced NSCLC (aNSCLC). We evaluated characteristics and outcomes of patients (pts) with RET+ aNSCLC.
Methods: This is an international, multicenter, retrospective study evaluating clinical, biological, pathological and radiological data of pts with RET+ aNSCLC. Objective response rates (ORR), duration of response (DOR) and progression-free survival (PFS) were evaluated under double or single agent chemotherapy (CT), immunotherapy (ICI), CT-ICI, multityrosine kinase inhibitors (MTKi) and RET inhibitors (RETi). Overall survival (OS) was calculated from the start of first line therapy and compared between pts treated or not by RETi, after stratification by number of treatment lines.
Results: A total of 71 pts was included from 11 centers. Median age was 60 [IQR 47-69], 58% were female, 93% had adenocarcinoma, 2 pts (3%) had squamous and 2 (3%) neuroendocrine carcinoma, 38 (53.5%) were tobacco consumers (median 18.5 PY [7.8-31.3]), 50 (70%) had stage IV disease at diagnosis. Fusion partners were KIF5B (35/49, 71%), CCDC6 (9/49, 18%), others (5/49, 10%). Median TMB was 2.76 [2.0-8.5], median PD-L1 5% [0-29]. The most frequent co-mutation was TP53 (18/58 cases, 31%). Median number of metastatic sites was 2 [1-3], most commonly lung (48%), bone (45%), pleura (41%) and nodes (35%). Brain metastases were found in 18% of cases at diagnosis and in 31% at last follow-up or death. Table reports outcomes by treatment. mOS was 50.6 months [95%CI 37.6 - NR]. Fifty-two pts received 1st generation RETi. The use of RETi improved OS in pts treated with ≤2 lines of therapy (NR vs 17.8 months, p=0.024) and in those receiving &gt;2 lines (50.6 vs 12.7 months, p=0.0037). Pts responding to ICI had a median PD-L1 of 85% [15.5-90].
Conclusions: Pts with RET+ aNSCLC have mainly thoracic and bone disease. Despite smoking history, median TMB and PD-L1 expression are low. ICI may have a significant activity in selected cases. RETi improve OS.
Outcomes by treatment First use of Doublet CT (N=46) Single agent CT (N=12) CT-ICI (N=9) ICI (N=19) MTKi (N=9) RETi (N=52) Line of treatment (median, range) 1 [1-1] 2 [2-3] 1 [1-2] 2 [2-3] 3 [1.5-3.5] 2 [1-3] ORR (N,%) 25/40 (62.5%) 3/12 (25%) 3/9 (33%) 7/17 (41%) 4/8 (50%) 36/45 (80%) mPFS (months, 95%CI) 7.89 [6.18-14] 2.81 [2.43-NR] 5.62 [2.79-NR] 3.71 [2.99-11.5] 2.76 [1.51-NR] 24.7 [16.2-NR] mDOR (months,95%CI) 11.83 [7.06-15.6] 8.90 [4.21-NR] 14.47 [10.25-NR] 20.47 [11.3-NR] 8.18 [1.64-NR] 24.74 [17.12-NR] Stopped for toxicity (N,%) 7/46 (15%) 1/12 (8%) 2/9 (22%) 4/18 (22%) 1/9 (11%) 14/50 (28%)
Citation Format: Mihaela Aldea, Arianna Marinello, Wael Zrafi, Fabrizio Tabbo, Florian Guisier, Damien Vasseur, Vincent Fallet, Clarisse Audigier-Valette, Laura Mezquita, Antonio Calles, Giannis Mountzios, Marco Tagliamento, Judith Raimbourg, Safae Terrisse, Silvia Novello, Maria-Rosa Ghigna, Fabrice Barlesi, David Planchard, Benjamin Besse. RET-MAP: An international multi-center study of patients with advanced non-small cell lung cancer and RET fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4019.