Uncommon EGFR mutations of lung adenocarcinoma in one tertiary institution, Korea: clinical characteristics and treatment response to tyrosine kinase inhibitors

Introduction: Adenocarcinoma is the most common type of non-small cell lung cancer (NSCLC) causing genetic mutations. The most common gene mutations associated with EGFR receptors are deletion at exon 19 and point mutation at exon 21, L858R. However, other uncommon mutations cover 10 to 18% of all EGFR mutations. We aimed to analyze uncommon EGFR mutations, compared to common mutation. Methods: EGFR mutation status in adenocarcinoma of NSCLC was investigated by retrospective analysis using the 2010-2016 chart review. Except for exons 19 and 21, 16 cases of uncommon mutations have been investigated. Results: Among the 370 subjects with adenocarcinoma, 144 (38.9%) had EGFR mutations, of which 128 (34.6%) had mutation at exons 19 and 21; 12 (3.2%) at exon 20 mutation; 4 (1.1%) at exon 18 mutation. Mean age, sex, and smoking history did not differ between EGFR (+) common and uncommon mutation. The median overall survival (OS) in EGFR (+) uncommon mutation of stage IIIb and above was 31.2 months, similar to 31.0 months in EGFR (+) common mutation. Whereas the OS in EGFR mutation (-) was 12.1 months. Among EGFR (+) uncommon mutation, only 5 cases (31%) presented ground-glass density nodules; 9 (69%) were nonsmokers; 12 were treated with tyrosine kinase inhibitors (TKIs). TKI response was observed in 8 (67%) and the mean treatment duration was 16 cycles. Conclusions: Uncommon EGFR mutations showed to respond favorably to known TKIs in two-thirds of Korean patients, unlike previous reports and showed similar survival rate to common mutations. TKIs may be selected as the first-line treatment for EGFR mutations at exon 18 and 20.