Third-line Treatment of Gefitinib in NSCLC Patients

• Primary Study Objective: To evaluate the disease control rate (DCR) of gefitinib as third-line retreatment in stage IIIB/IV NSCLC with EGFR 19del/L858R positive mutation patients who had benefited from first-line gefitinib treatment with EGFR 19del/L858R positive mutation and tumor progression after the second-line chemotherapy
• Secondary Study Objectives: To evaluate objective response rate (ORR), progressive-free survival (PFS), overall survival(OS) and quality of life (QoL) of gefitinib as third-line retreatment in NSCLC patients To evaluate the safety of gefitinib as third-line treatment in NSCLC patients
• Exploratory analyses: To dynamically monitor EGFR mutation status and explore the relationship with clinical outcome

Inclusion criteria

• The subject or legal guardian could understand and sign informed consent form.
• Male or female aged 18 years or older;
• Subjects were diagnosed with stage IIIB or IV NSCLC before starting the first dose of gefitinib third-line treatment;
• EGFR exon 19 deletion or exon 21 L858R substitution mutation confirmed;
• ECOG performance status 0-2;
• Life expectancy of at least 12 weeks or longer;
• Has at least one measureable lesion by RECIST 1.1;
• NSCLC of enrolled subjects previously progressed after first-line gefitinib treatment (PFS ≥ 6 months) and progressed again after second-line chemotherapy (not limited for chemotherapy regimen, ≥ 4 cycles of chemotherapy). Investigator considers adopting third-line gefitinib retreatment;
• Criteria for laboratory examinations:

• Total bilirubin (TB) ≤ 1.5 times upper limit of normal
• Aspartate aminotransferase(AST), alanine aminotransferase (ALT) ≤2 times upper limit of normal; for subjects with hepatic metastasis, AST,ALT≤ 5 times upper limit of normal
• Creatinine clearance≥45ml/min

Exclusion criteria

• Known severe hypersensitivity to gefitinib or any ingredients of the product;
• Patients with prior exposure to agents directed at the EGFR axis except gefitinib (e.g. erlotinib, cetuximab, trastuzumab) ;
• Pre-existing interstitial lung disease or pulmonary fibrosis evidenced by CT scan at baseline;
• Neutrophil count <1.0×109/L or platelet count <50×109/L;
• Severe infection, uncontrolled systemic disease (e.g cardiopulmonary insufficiency, fatal arrhythmias, hepatitis, etc);
• Pregnancy or breast-feeding;
• Women of childbearing age refuse to take adequate contraception measures during gefitinib treatment
• Subjects with other malignant tumors combined;
• Known or suspected brain metastases or spinal cord compression, unless treated with surgery and/or radiation and stable without steroid treatment for at least 4 weeks prior to the first dose of study medication;
• Subjects are unable to take medications orally or have digestive malabsorption;
• Investigators consider subjects should not be involved in the study.