Recurrence Patterns In Patients With Advanced Non-small Cell Lung Cancer After Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Background:Lung cancer is the leading cause of cancer death worldwide in both men and women. With urban industrialization and rural urbanization, the incidence and mortality of lung cancer is rising and lung cancer has become the leading cause of death for urban residents. Lung cancer is divided into non-small cell lung cancer (non-small lung cancer, NSCLC) and small cell lung cancer (small cell lung cancer, SCLC) according to its pathological features. Non-small cell lung cancer (NSCLC) accounts for80%of all lung cancer. A number of patients haves tage ⅢB or Ⅳ disease at the time of diagnosis. Platinum-based combination therapy has been the treatment base for advanced NSCLC. However, the1-year survival rate is only30%-40%, with a median survival (8-10months). Therefore the request of more effective treatment of advanced or metastatic NSCLC has become a challenge worldwide.Gefittinib and erlotinib are small molecule reversible inhibitors of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) that have demonstrated efficacy in patients with relapsed NSCLC and as initial therapy for patients with advanced NSCLC and sensitizing EGFR mutations. Despite the initial dramatic responses and substantial progression free survival (PFS) to EGFR TKI observed in various clinical trials, most of NSCLC patients with EGFR-activating mutation ultimately developed local progression or metastases. However, there is an incomplete data about the progression patterns in the NSCLC patients treated with EGFR-TKIs.Objective:This retrospective study was undertaken to investigate the recurrence patterns in the NSCLC patients treated with EGFR-TKIs with EGFR-activating mutation.Materials and Methods:1. We reviewed the medical records and imaging findings of52NSCLC patients with sensitizing EGFR mutations at Shandong Provincial Hospital between2010and2013.2. During the study period, eligible patients received oral gefitinib250mg or erlotinib150mg once daily until the disease progressed.3. The initial failure sites of52EGFR-TKIs treated patients with III/IV NSCLC and were reviewed.4. The primary endpoint of this study was to analyze the initial failure sites of the patients treated with EGFR-TKIs.The secondary endpoint was to assess progression-free survival (PFS). The PFS was calculated from the initiation of EGFR-TKI treatment until the progression of disease. Survival curves were made according to the Kaplan-Meier method.Results:1. The median age of52patients treated with EGFR-TKIs was57years old (range,37-80years old). The median progress free survival (PFS) was8months.2.51of the52patients had single-site relapse,1patient displayed multi-sites relapse. For19of the52patients, the progression occurred in pre-existing disease, the other patients developed new disease. Intrapulmonary progression occurred in20patients and extrapulmonary progression occurred in31patients,1patients had disease recurrence in both intrapulmonary and extraplumonary sites.16patients had CNS failure, including six cases of pre-existing lesions and ten cases of new lesions.3. The first sites of disease recurrence were lung (38.46%),central nervous system (CNS)(30.77%), bone (17.31%), etc. 4. Patients with lung failure had a shorter median PFS time(6months vs.8months. P=0.01014). Patients who had CNS metastasis as initial site of progression had a relatively longer median PFS time(10months vs.8months. P=0.028).Conclusion:The lung and the CNS were the most common recurrence sites in EGFR-TKIs treated patients with stage ⅢB/Ⅳ NSCLC harboring a somatic EGFR mutation. It’s useful to monitor the lung and brain for early detection of disease recurrence.