1. Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China
2. Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China
3. Hubei Clinical Cancer Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China
*Contributed equally to this work.
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.
Keywords: non-small cell lung cancer, epidermal growth factor receptor, T790M, tyrosine kinase inhibitor, risk factors