Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinumbased chemotherapy

Objective: Data on the clinical activity of epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors(TKIs) in patients with non-small-cell lung cancer(NSCLC) and uncommon EGFR mutations remain insufficient.This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations.Methods: We retrospectively enrolled 504 patients with EGFR-mutant NSCLC.The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC.Results: Seventy patients(13.9%) harboring uncommon EGFR mutations were included.Thirty of these patients received EGFR-TKIs and 40 received platinum-based chemotherapy as first-line therapy.The objective response rate(ORR) and median progression-free survival(m PFS) of patients treated with TKIs in the uncommon mutation group was significantly inferior to that in the common mutation group(ORR: 23.3% vs.51.8%,P=0.003; m PFS:7.1 vs.10.9 months,P<0.001).In the uncommon group,m PFS was similar between first-line EGFR-TKIs treatment and platinum-based chemotherapy(7.1 vs.6.1 months,P=0.893).In patients with EGFR G719 X or L861 Q mutations,the m PFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group,but the difference was not statistically significant(G719 X: 8.2 vs.5.8 months,P=0.061; L861 Q: 7.6 vs.4.1 months,P=0.872).Multivariate analyses identified adenocarcinoma(P=0.003) as the independent predictive factor for PFS in patients with uncommon EGFR mutations who were treated with first-line EGFR-TKIs.Conclusions: The current study demonstrated that the effect of first-line EGFR-TKIs was similar to that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC.Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR-mutant NSCLC patients treated with first-line EGFRTKIs.