Real-world outcomes of chemoimmunotherapy and selective RET inhibitors in Chinese patients with RET fusion-positive non-small cell lung cancer

• Published in: Heliyon 2024-01, Vol.10 (2), p.e24796-e24796, Article e24796
• Main Authors: Wan, Rui, Li, Weihua, Wang, Zhijie, Zhong, Jia, Lin, Lin, Duan, Jianchun, Wang, Jie
• Format: Article
• Language: English
• Subjects: disease control; females; gene fusion; Immunotherapy; Lung cancer; lung neoplasms; RET fusion; RET inhibitors; retrospective studies; Targeted therapy; transfection
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e24796

Rearranged during transfection (RET) gene fusion is a target for non-small cell lung cancer (NSCLC) treatment, and RET inhibitors are approved for advanced NSCLC. The role of immune checkpoint inhibitors (ICIs) in RET fusion-positive NSCLC remains controversial. This retrospective study analyzed the efficacy of ICIs and RET inhibitors in Chinese patients with RET fusion-positive NSCLC. Data from patients diagnosed with advanced NSCLC harboring RET fusion from Jan 2017 to Sep 2021 were analyzed. Clinicopathological characteristics and outcomes of ICIs and RET inhibitors treatments were collected. Seventy-five patients with RET fusion-positive advanced NSCLC were identified. The median age of patients was 57 years, half of the patients were female (50.3%), and most were non-smokers or light smokers (72%). Of the cancer types diagnosed in study patients, the KIF5B-RET fusion subtype accounted for 73.3% (55/75), twelve patients (16%) had CCDC6-RET fusion, and three (4%) had NCOA4-RET fusion. Sixteen patients were treated with ICIs. In previously untreated patients, we observed an objective response rate (ORR) of 71.4% and median progression free survival (PFS) of 7.5 months in seven assessable patients. Of four patients with PD-L1 overexpression (>50%) one received pembrolizumab and the other three patients received pemetrexed, carboplatin, and pembrolizumab or camrelizumab. In these patients, the ORR was 75% and disease control rate was 100%. Fifteen patients received selective RET inhibitors (pralsetinib and selpercatinib), resulting in an ORR of 53.3% (8/15) and median PFS of 10.0 months (95% CI 5.2–14.9). ICIs for PD-L overexpression and treatment naive patients offer comparable benefits for RET fusion-positive NSCLC, warranting further investigation. •Relatively high proportion of PD-L1 expression in RET fusion-positve lung cancer.•RET fusion-positve patients with PD-L1 overexpression may benefit from chemoimmunotherapy.•Selective RET inhibitors displayed superior efficacy compared to cabozantinib.•KRAS mutation and EGFR amplification may mediates RET inhibitors resistance.