Clinicopathologic features of nrg1 fusion-positive non-small cell lung cancer

Abstract

Data on the clinicopathological features of NRG1 fusion?positive non?small cell lung cancer (NSCLC) are limited. We conducted a retrospective, multicenter study and included patients with NRG1 fusion?positive NSCLC diagnosed between January 2018 and February 2025. Six patients were identified; five were female (83.3%), two were never?smokers (33.3%), and four were former smokers (66.7%). Adenocarcinoma was the predominant histology ( n = 5), comprising mucinous ( n = 2), enteric ( n = 2), and not otherwise specified ( n = 1) variants, while one patient had squamous cell carcinoma. All were PD?L1–negative, and CD74?NRG1 was the most common fusion (50%). Three patients received afatinib; only one achieved a partial response with a progression?free survival of 8.7 months. Median overall survival was 6.7 months. Our study demonstrates the histologic and molecular heterogeneity of NRG1 fusion?positive NSCLC, encompassing mucinous and enteric variants of adenocarcinoma. Responses to afatinib were variable, underscoring the need for more effective therapies, including zenocutuzumab and emerging agents.