Introduction

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the established first-line standard of treatment for EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). The uncommon mutations in currently available EGFR TKIs are widely heterogeneous and less well known. There are limited clinicopathologic data available in patients with NSCLC harboring uncommon EGFR mutations in Korea

Methods

We retrospectively analyzed the NSCLC patients among the lung cancer cohort of the Catholic Medical Center of Korea between January 2018 and December 2021. 

Results

In 589 EGFR mutation harboring NSCLC patients, 76 (12.9%) were patients with uncommon mutations. The composition of uncommon mutations was identified as follows: exon 20 insertion (19.7%), ?major? uncommon mutations (50.7%), compound mutations (13.7%) and other mutations (35.6%). The progression free survival (PFS) was shorter in patients with uncommon EGFR mutations compared to patients with common mutations (843.9±58.6 vs. 517.4±118.1, P=0.001). The proportion of male (38.6% vs. 53.9%, P=0.011), squamous cell type (2.5% vs. 11.8%, P=0.001), COPD (16.6% vs. 33.3%, P=0.003) were higher, but that of never smoker (63.0% vs. 43.4%, P=0.005) was lower in patients with uncommon EGFR mutations. The mean values of SP263 (10.7 vs. 16.5, P=0.015), total lung capacity (94.9±16.4 vs. 102.4±47.9, P=0.015), residual volume (85.9±28.5 vs. 99.8±107.9, P=0.001) were higher. 

Conclusion

The uncommon EGFR mutations had unique clinicopathologic characteristics including smoking tendency, gender preference, and PD-L1 expression. Further investigations are needed to confirm the responsiveness of immunotherapy in the subgroups.