Non-small cell lung cancer harbouring non-resistant uncommon EGFR mutations: Mutation patterns, effectiveness of epidermal growth factor receptor-tyrosine kinase inhibitors and prognostic factors.

INTRODUCTION

Non-small cell lung cancer (NSCLC) harbouring EGFR exon 19 deletions or L858R mutation usually respond to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), whereas T790M mutation and exon 20 insertion are frequently resistant to EGFR-TKIs. EGFR mutations other than those above are seldom investigated.

METHODS

In this multicentre, retrospective study, we enrolled NSCLC patients with non-resistant uncommon EGFR mutations, which were defined as mutations other than L858R, exon 19 deletions, exon 20 insertions and T790M. The mutation patterns, clinical data and treatment outcomes were analysed. Patients were classified as gefitinib/erlotinib and afatinib groups according to the EGFR-TKIs received as the first-line therapy.

RESULTS

A total of 177 patients were identified (177/1983, 8.9%). Sixty-six patients had more than one EGFR mutation, including those coexisting with exon 19 deletion or L858R mutation. In treatment-naïve patients with advanced stages (n = 72), the objective response rate was 35.8% for gefitinib/erlotinib group and 60.6% for afatinib group (p = 0.036). In multivariate analysis, no significant differences were found between gefitinib/erlotinib and afatinib groups in median progression-free survival (PFS) and overall survival (OS). Brain metastasis at diagnosis was associated with a shorter PFS (hazard ratio [HR] = 2.49, 95% confidence interval [CI] = 1.29-4.83) and OS (HR = 3.22, 95% CI = 1.41-7.35).

CONCLUSIONS

For patients with NSCLC harbouring non-resistant uncommon EGFR mutations, afatinib use as the first-line therapy may provide a better treatment response but no survival benefit, as compared with gefitinib or erlotinib. Brain metastasis at diagnosis is associated with a poor prognosis.