Clinicopathologic characteristics and outcome of patients with different EGFR mutations

Abstract

Aim: Most epidermal growth factor receptor (EGFR) gene mutations affecting exon 19 (inframe deletions; 19 Del) and 21 (L858R), while the rest (referred as uncommon EGFR mutation) have not been fully described due to their rarity. Here we present a retrospective study that investigated clinical characteristics and outcome of patients with different EGFR mutations.

Methods: We retrospectively analyzed the EGFR mutation pattern and its association with clinical-pathological characteristics from 100 cases of nonsmall-cell lung cancer (NSCLC) harboring EGFR mutations, and compiled the genotype response data for NSCLC patients with common and uncommon EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs). Patients with advanced EGFR-mutated NSCLC were enrolled and treated with icotinib (oral administration, 125 mg, thrice per day).

Results: Among 100 patients, 85 and 15 had common and uncommon mutations, respectively. Four patients had a single mutation in 18 or 20 exon, and 11 had a complex mutation with del-19 or L858R. There was no significant association between the presence of different mutation type and the type of any clinical and pathological characteristics. Prolonged but not significant progression-free survival (PFS) was noted in patients with common EGFR mutations (18.07 [14.00-26.23] vs 12.9 [8.43-23.27], P = 0.056). Patients without brain metastases had increased PFS to icotinib than those with brain metastases (18.07 [95% confidence interval, CI 14.77-27.03] vs 13.17 [95% CI 8.63-22.63], P = 0.038).

Conclusion: Uncommon EGFR mutations comprised 15% of all mutated patients, in which most were complex mutations. Compared with common EGFR mutation, uncommon EGFR mutations were associated with a modest sensitivity to EGFR TKIs. Our findings will be helpful to make clinical decision and select the appropriate therapy for EGFR-mutated NSCLC patients.

Keywords: EGFR-tyrosine kinase inhibitors; icotinib; nonsmall cell lung cancer; uncommon EGFR mutations.