Abstract 31P
Background
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy are the core options for advanced non-small cell lung cancer (NSCLC) treatment. The efficacy of EGFR-TKI therapy was shown to vary depending on sex. And furthermore, EGFR alterations can impact PD-L1 expression and immunotherapy benefits. The aim of this study was to investigate the prevalence of clinically actionable EGFR mutations and their relation to PD-L1 expression with respect to gender in the Ukrainian cohort.
Methods
This retrospective study included 907 patients, diagnosed with advanced NSCLC who were tested for EGFR mutations and PD-L1 expression. There were 797 patients (87,9%) with adenocarcinoma (AC), 101 patients (11,1%) with squamous cell carcinoma (SCC) and 9 individuals (1%) with large cell neuroendocrine carcinoma (LC-NEC). EGFR mutation status in tissue samples was assessed by either NGS (n = 83) or qPCR (n = 824). PD-L1 testing was performed by IHC.
Results
SCC rate was higher in males (13,3% vs 8,4%), females demonstrated prevalence of AC (91,1% vs 85,3%; P = 0,022). 78 (21,5%) out of 363 women with AC were under 50 y.o., while only 65 out of 434 (15%) men were younger than 50 at the time of AC diagnosis (P = 0,027). 198 out of 907 patients (21,8%) had EGFR-mutant NSCLC. Patients with AC harbored EGFR mutations twice as frequently (187 out of 797 patients; 23,5%) as compared to SCC (9 out of 101; 8,9%; P = 0,004). There was no statistically significant difference in PD-L1 expression between NSCLC of different histology and EGFR status. EGFR mutation rate was higher in females (35,5%) compared to males (11,2%; P < 0,001). The Ex19del and L858R variants predominated in both males and females. However, females demonstrated a higher rate of sensitizing EGFR mutations (87,9% vs 71,9% in males). Males with NSCLC carried more exon 20 alterations, including in-frame insertions and T790M mutation (15,8% vs 4,3% in females) and presented uncommon variants including G719X, L861Q and S768I (10,5% vs 4,3%) more frequently (P = 0,009).
Conclusions
There are profound gender differences in the rates and spectrum of EGFR mutations in NSCLC with no relation to PD-L1 expression. Gender differences in EGFR mutation landscape can affect response to treatment.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.