23P Clinical impact and prognostic value of EGFR mutation co-occurring with ALK, ROS1, RET fusions, or MET exon 14 skipping mutations in Chinese patients with non-small cell lung cancer

The concurrence of EGFR mutations with ALK, ROS1, RET fusions, or MET exon 14 skipping mutations is rare in non-small cell lung cancer (NSCLC) and lacks reliable predictive biomarkers. This study aims to evaluate the prevalence, clinical characteristics, and prognostic factors of these co-mutations in a Chinese NSCLC cohort. A retrospective analysis of 3,669 pathologically confirmed NSCLC patients (2020–2023) was conducted. High-throughput sequencing was used to identify co-mutations of EGFR with ALK, ROS1, RET fusions, or MET exon 14 skipping mutations in tissues. Correlation analyses were performed between these co-mutations and clinicopathological parameters, as well as survival outcomes. Co-mutations were identified in 42 patients, including EGFR-ALK fusions (n=22), EGFR -ROS1 fusions (n=5), EGFR-MET exon 14 skipping mutations (n=3), and EGFR-RET fusions (n=12). These patients had a median age of 60.5 years, and 92.9% were diagnosed with adenocarcinoma. Patients with co-mutations had a lower incidence of smoking (26.2% vs 49.0%, p<0.01) and a higher proportion of advanced-stage disease (64.3% vs 47.0%, p<0.05) compared to patients without co-mutations. The EGFR-RET co-mutation group had a higher proportion of patients aged ≤ 60 years (83.3%) compared to other groups (p<0.05). The median overall survival (OS) for the 25 stage IV patients treated with tyrosine kinase inhibitors (TKIs) was 25 months. No significant difference was found in OS between mono-targeted and dual-targeted therapy groups, or among different co-mutation groups. Superior OS was observed in non-smokers compared to smokers (HR=7.9, p<0.001), in females compared to males (HR=3.6, p=0.019), and in early-stage patients (I-II) compared to advanced-stage patients (III-IV) (HR=3.88E+08, p=0.002). This study highlighted the occurrence and clinical characteristics of EGFR-involved co-mutations in a Chinese NSCLC cohort. Non-smoking, female gender, and younger age were identified as favorable prognostic factors in this co-mutated population.