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The meta-analysis evaluated the efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the treatment of non-small cell lung cancer (NSCLC). The PubMed/MEDLINE, Ovid, Web of Science, CNKI, and the Cochrane Library database were searched for eligible randomized controlled trials comparing the combination of chemotherapy or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with bevacizumab to chemotherapy or EGFR-TKI alone. Main outcome measures were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse effects. The pooled data were analyzed by STATA 12.0 and expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95 % confidence intervals (95 % CI). Nine eligible trials comprising 3,547 patients (1,779 for bevacizumab and 1,768 for controls) were included in the study. Chemotherapy or TKIs in combination with bevacizumab significantly prolonged PFS (HRpfs 0.72, 95 % CIpfs 0.66-0.79, P pfs < 0.001) and OS (HRos 0.90, 95 % CIos 0.82-0.99, P os = 0.029) as first-line treatment for NSCLC compared with chemotherapy or TKIs alone. Bevacizumab combination regimens significantly prolonged PFS (HR 0.62, 95 % CI 0.52-0.74, P < 0.001) as second-line treatment; however, no benefit regarding OS was observed with the addition of bevacizumab (HR 0.94, 95 % CI 0.78-1.12, P = 0.479). The bevacizumab group showed increased ORR in both first- and second-line treatments. The high-dose bevacizumab subgroup in combination with chemotherapy showed a statistically significant improvement in OS, PFS, and ORR (HRos 0.89, 95 % CIos 0.80-0.99, P os 0.037; HRpfs 0.71, 95 % CIpfs 0.64-0.79, P pfs < 0.01, RRorr 1.85, 95 % CIorr 1.59-2.15, P orr < 0.001, respectively); however, the low-dose bevacizumab subgroup did not show enhanced OS (HRos 0.91, 95 % CIos 0.77-1.07, P os = 0.263), and a moderate improvement of PFS and ORR (HRpfs 0.85, 95 % CIpfs 0.72-1.00, P pfs = 0.049; RRorr 1.60, 95 % CIorr 1.28-2.0, P orr < 0.001). Erlotinib in combination with bevacizumab significantly prolonged PFS (HR 0.60, P < 0.001, 95 % CI 0.51-0.71) and increased ORR (RR 1.21, 95 % CI 0.98-1.49, P = 0.067) compared with erlotinib alone. A higher incidence of grade ≥3 adverse events such as proteinuria, hypertension, and hemorrhage was observed in the bevacizumab combination group than in the control group without bevacizumab (P all < 0.05). The addition of bevacizumab to chemotherapy or erlotinib can significantly improve PFS and ORR both in first- and second-line treatments of advanced NSCLC, with an acceptable risk of bleeding events, hypertension, proteinuria, and rash. Combination therapy with bevacizumab and chemotherapy is beneficial regarding OS; however, whether bevacizumab plus erlotinib can prolong OS need further validation.

This study aimed to detect mutations in EGFR and KRAS and alterations of c-Met gene copy number (GCN) changes in primary and lymph node-metastatic NSCLCs. The data showed the concordant rate of EGFR genotype in primary and stage N2 lymph node-metastatic tumors was 95.45%. c-Met GCN in stage N2 lymph nodes was significantly higher than that of the primary tumors (P=0.038). The results suggest both primary and lymph-node metastases have relatively consistent EGFR mutations and EGFR mutations are not relevant to changes in c-Met GCN. c-Met GCN was increased significantly in EGFR TKI-naive patients with lymph node-metastatic tumors., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to detect the pre- and post-treatment serum carcinoembryonic antigen (CEA) levels after 4 weeks of EGFR-TKIs treatment in advanced non-small cell lung cancer (NSCLC) patients to evaluate the clinical value of CEA in the prediction of chemotherapy response and prognosis in those patients., Methods: Pre- and post-treatment serum CEA levels of the patients were measured with immunoradiometric kits after 4 weeks of EGFR-TKIs treatment to evaluate the relationship between chemotherapy response and prognosis., Results: After 4 weeks of EGFR-TKIs treatment, one patient in the total of 75 patients (1.3%) achieved complete response (CR), 17 patients (22.7%) achieved partial response (PR), 31 patients (41.3%) achieved disease stable (SD) and 26 patients had progressive disease (PD). The radiological objective response rate(ORR) and disease control rate (DCR) were 24.0% and 65.3%, respectively. The median survival time (MST) of all patients was 8.1 months. The MST of SD patients was similar to that in the OR patients (P = 0.06), but both longer than that in the PD patients (P < 0.001). The MST of DC patients was similar to that in OR patients (P = 0.358), but longer than that in PD patients (P < 0.001). Serum CEA levels decreased ≥ 32% and ≥ 61% were closely related with the objective response and disease control. The median survival time (MST) of patients with serum CEA decreased ≥ 32% was longer than those with CEA decreased < 32% (9.5 months vs 6.7 months, P < 0.0001). The MST of patients with serum CEA decreased ≥ 32% was similar to those with CEA decreased ≥ 61% (9.5 months vs 10.5 months, P = 0.370), but both longer than those with CEA decreased < 32% (6.7 months, P < 0.001). Cox multivariate survival analysis confirmed that serum CEA level decreased ≥ 32%, CEA level decreased ≥ 61%, PS score, and DC are independent prognostic factor, but not OR., Conclusions: To advanced NSCLC patients, the disease control rate (DCR) may be more suitable than objective response rate (ORR) as an indicator in predicting the efficacy and prognosis in advanced NSCLC patients. Serum CEA levels decreased ≥ 32% may be a reliable indicator to determine the therapeutic efficacy of EGFR-TKIs.