anlotinib hydrochloride combined with egfr tkis in advanced non-small cell lung cancer

Conditions: Non-Small-Cell Lung

Summary: after the second-line treatment of patients with non-t790m mutations, chemotherapy with platinum-containing drugs was used, and chemotherapy-related toxicity was high. studies have shown that bevacizumab combined with egfr tki have a good trend of benefit. this study is aimed to evaluate the efficacy and safety of anlotinib hydrochloride combined with first-generation egfr tkis as second-line treatment in advanced non-small cell lung cancer . the patients with iv non-small lung cancer have acquired resistance to prior first-generation egfr tkis and have non-t790m mutation.


Eligibility criteria:
inclusion criteria: * participants must have histlogically confirmed stage iv non-small cell lung cancer . * the initial treatment with gefitinib/icotinib evaluated pr/nc and the efficacy lasted for more than 6 months, then the disease progressed later. (the efficacy was assessed as pd according to the evaluation standard of recist1.1) * at least a measurable lesion that meets the recist 1.1 criteria. * any gender. age ≥18 years and ≤75 years * life expectancy \>3 months. * eastern cooperative oncology group (ecog) performance status 0-1. * previously, egfr gene test showed egfr exon 19 deletion or exon 21 (l858r) mutation, and the gene test showed no t790m mutation before enrollment. * adequate organ function: haemoglobin ≥ 90 g/l;neutrophils count ≥1.5×109/l; platelet count ≥ 90 × 109/l; total bilirubin ≤ 1.5 × uln ;alt \< 2 × uln, (alt \< 5 × uln, for those with liver metastases);ast \< 2 × uln, (ast \< 5 × uln, for those with liver metastases); cr≤1.5× uln. * echocardiography : lvef≥50% * 12-leads electrocardiogram : qtcf\<450ms (man), \<470ms(woman) * patient informed consent and signed written consent * patient compliance was good and voluntary follow-up, treatment, laboratory testing, and other research steps were performed as planned. exclusion criteria: * the patient has previously received anti-tumor therapy for egfr tkis other than gefitinib and ectinib for lung cancer. * patients that cannot detect egfr gene, or patients with known t790m mutation. * small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer). * ct or mri shows that the tumor lesion is ≤ 5 mm from the large vessel, or there is a central tumor that invades the local large blood vessel; or there is a significant pulmonary cavity or necrotizing tumor. * active brain metastasis, cancerous meningitis, spinal cord compression patients. * other active malignancies that require simultaneous treatment. * has a history of malignant tumors in the past 5 years. * patients with previous anti-tumor treatment-related adverse reactions who have not recovered to nci-ctc ae≤1. * abnormal coagulation ,with bleeding tendency or undergoing thrombolysis or anticoagulant therapy. * renal insufficiency: urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g, or creatinine clearance \<60ml / min. * severe acute or chronic infection requiring systemic treatment. * suffering from severe cardiovascular disease: myocardial ischemia ,myocardial or arrhythmia. * clinically significant hemoptysis occurred within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or a clear tendency to hemorrhage. * untreated active hepatitis : hepatitis b or hepatitis c