Risk factors of acquired T790M mutation in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer

Background: It is still controversial to employ osimertinib as the first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC) patients in practice. The aim of the current study was to explore the risk factors of acquired T790M mutation during EGFR-TKIs therapy, and to identify the potential patients most likely to benefit from first-line osimertinib treatment. Methods: A total of 222 patients with EGFR-mutated (non-T790M) advanced NSCLC were analyzed. The progression-free survival (PFS), overall survival (OS), and cumulative incidence of acquired T790M mutation were calculated with the Kaplan-Meier method. The independent risk factors were investigated with the multivariate analysis. Results: A total of 70 patients acquired T790M mutation and were treated with osimertinib as a second-line treatment. These patients showed a significantly better OS (P=0.003) than those without T790M mutation. Multivariate analysis indicated that BMI ≤ 25 (P= 0.031), NSE > 17.9 ng/ml (P= 0.013) before treatment, and retroperitoneal lymph node (LN) metastasis (P= 0.002) were independent risk factors of acquired T790M mutation. At last, the actuarial risks of acquired T790M mutation at 1 year after EGFR-TKI treatment were 6.6% in patients with 0-1 risk factor and 31.5% in patients with 2-3 risk factors. Conclusions: Patients developing acquired T790M mutation during EGFR-TKI treatment had a better OS of osimertinib treatment. Lower BMI, higher NSE before treatment, and retroperitoneal LN metastasis are independent risk factors of acquired T790M mutation. Our study suggested that patients with 2-3 risk factors were highly recommended the first-line osimertinib treatment.