5440 - Different stories for different EGFR exon 19 deletion variants

Background

Epidermal growth factor receptor (EGFR) exon 19 deletion (19del) and L858R mutation respond differently to first generation tyrosine kinase inhibitors (TKIs), however, the clinical outcomes of different 19del variants to TKIs and the resistance patterns are not well studied.

Methods

From April 2016 to August 2017, 194 treatment-naive NSCLC patients detected as EGFR exon 19 deletions using amplification-refractory mutation system were included. DNA sequencing was used to detect the subtypes. Clinicopathological features as well as patients’ outcomes to first-line EGFR TKIs were analyzed.

Results

Twelve EGFR 19del variants were confirmed in 169 of the 194 samples. Among these, p.E746_A750del was the most frequent variant (147/169, 87.0%). p.E746_A750del was more frequently found in females (p = 0.008) and never smokers (p = 0.004) than other deletions. And deletions starting with E746 was also more frequently found in these patients than L747 (p = 0.014 and p = 0.018, respectively). Interestingly, T790M occurred more frequently in p.E746_A750del than other deletions (64.3% vs 18.2%, p = 0.017) or deletions started with E746 than L747 (63.6% vs 11.1%, p = 0.012). Patients harboringdeletions starting with L747 plus insertions had significantly shorter progression-free survival (PFS) than no insertions (8.3m vs 15.0m, p = 0.008), as well as other subtypes (8.3m vs 12.8m, p = 0.016). Multivariate analysis showed that only L747 deletion plus insertions and age were independent factors influencing PFS (p = 0.015 and 0.046, respectively).

Conclusions

p.E746_A750del was the most frequent variant of EGFR exon 19del in NSCLC patients. It was more frequently found in female and never smoking patients. T790M mutation had a higher ratio in these patients when they were resistant to first-line TKI treatment. Deletions starting with L747 plus insertions had shorter PFS than other variants.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.