Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinum-based 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 (mPFS) 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; mPFS: 7.1 vs . 10.9 months, P<0.001). In the uncommon group, mPFS 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 G719X or L861Q mutations, the mPFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group, but the difference was not statistically significant (G719X: 8.2 vs . 5.8 months, P=0.061; L861Q: 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 EGFR-TKIs.