Clinical features and outcomes of unresectable locally advanced lung adenocarcinoma with uncommon EGFR mutations: a retrospective multi-center Chinese study

Uncommon epidermal growth factor receptor (EGFR) gene mutant locally advanced non-small cell lung cancer (NSCLC) has been poorly documented in the literature. Our study aimed to investigate the clinical features and outcomes associated with these mutations. A multi-center retrospective study was conducted to review 511 patients with EGFR mutant unresectable stage III lung adenocarcinoma, treated between 2012 and 2018 across 12 Chinese institutions. The patients were categorized into three groups based on their primary treatment: chemoradiotherapy (CRT), EGFR-TKIs (tyrosine kinase inhibitors), and radiotherapy (RT) combined with EGFR-TKIs. Among the 511 patients, 49 (9.6%) had uncommon EGFR mutations. Of these, 37 had detailed systemic treatment information. The uncommon mutations included exon 18 G719X (22.4%), exon 20 insertion (18.4%), exon 20 S768I (8.2%), T790M (8.2%), and exon 21 L861Q (4.1%). Compound mutations were identified in 34.7% of patients. There was a significant difference in progression-free survival (PFS) for uncommon and common mutation group (median 11.9 vs. 17.5 months, P=0.005). However, no significant difference was observed in overall survival (OS, P=0.14). The median PFS for the uncommon mutation group was 11.9 months for CRT (n=12, 32.4%), 5.0 months for EGFR-TKIs (n=16, 43.2%), and 14.8 months for RT combined with TKIs (n=9, 23.4%) (P=0.02). The median OS for the same groups were 43.6 months, 30.9 months, and not reached, respectively (P=0.18). Compared to EGFR-TKIs, both CRT and RT combined with TKIs significantly improved PFS (P=0.02, 0.04, respectively), and showed a trend toward superior OS compared to EGFR-TKIs (P=0.49, 0.06, respectively). This study was the first to systematically summarize the clinical features and outcomes of unresectable locally advanced lung adenocarcinoma, with uncommon EGFR mutations. RT combined with sensitivity EGFR-TKIs may be a promising treatment option, while CRT remains the primary treatment choice.