Purpose: To explore the efficacy and safety of the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) Osimertinib in the treatment of patients with first-generation EGFR-TKI-resistant advanced non-small cell lung cancer (NSCLC).
Methods: The clinical data of 84 patients with advanced NSCLC treated in our hospital from September 2016 to March 2018 were retrospectively analyzed. All patients had progressive disease (PD) after treatment with first-generation EGFR-TKI, and then they were treated with Osimertinib. The remission of disease was analyzed and evaluated after treatment, and the long-term survival and progression of disease were recorded via follow-up. The influencing factors for the patient's prognosis were explored using univariate and multivariate Cox regression analyses.
Results: The efficacy was evaluated in all patients at 4 weeks after treatment. There were 0 cases of complete response (CR), 34 cases (40.5%) of partial response (PR), 38 cases (45.2%) of stable disease (SD) and 12 cases (14.3%) of PD. The objective response rate (ORR) and the disease control rate (DCR) were 40.5% (34/84) and 85.7% (72/84), respectively. The main adverse reactions included diarrhea (34.5%), nausea and vomiting (14.3%), constipation (11.9%), rash (27.4%), skin itch (20.2%), loss of appetite (13.1%), oral ulcer (10.7%), hepatic dysfunction (2.4%) and bone marrow suppression, mostly of grade I-II, which could be significantly relieved after symptomatic treatment. The incidence rate of grade III and above adverse reactions was 9.5% (8/84). The dosage of Osimertinib was reduced in 2 cases due to adverse reactions, while other adverse reactions were improved after symptomatic treatment. The levels of vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) obviously declined from 247.57±20.72 pg/mL and 11.20±1.38 μg/L before treatment to 134.84±14.37 pg/mL and 6.80±0.54 μg/L after treatment (p<0.05). The median overall survival (mOS) and median progression-free survival (mPFS) were 25.3 and 10.6 months, respectively. The 1-year OS rate was 79.8% (67/84), and the OS rate was 52.3% at the end of follow-up. Subgroup analysis showed found that heart disease and thrombosis complicated before treatment had significant impact on mOS (p=0.007, p=0.019). The results of multivariate Cox regression analysis revealed that heart disease and thrombosis complicated before treatment were independent risk factors affecting the patient's OS [HR=2.339 (95% CI: 1.448-5.674), p=0.031, HR=1.977 (95% CI: 1.152-2.365), p=0.020].
Conclusion: Osimertinib has definite efficacy in the treatment of patients with first-generation EGFR-TKI-resistant advanced NSCLC, with a low incidence rate of tolerable adverse reactions. The presence or absence of heart disease and thrombosis before treatment are independent influencing factors for the patient OS.