title: Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis.
abstract: Bevacizumab and erlotinib inhibit different tumour growth pathways, and both exhibit beneficial effects in the treatment of non-small-cell lung cancer (NSCLC). However, the efficacy of bevacizumab in combination with erlotinib remains controversial. Therefore, we conducted a meta-analysis to compare combination treatment with bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in the treatment of NSCLC.
  
  
  
  Randomised controlled trials (RCTs) published in PubMed, Web of Science and EMBASE were systematically reviewed. The main outcome measures included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and adverse events. Results were expressed as HRs or risk ratios (RRs) with 95% CIs.
  
  
  
  5 RCTs involving a total of 1736 patients were included in this meta-analysis. The combination of bevacizumab and erlotinib significantly improved PFS (HR=0.63, 95% CI 0.53 to 0.75; p=0.000) and the ORR (RR=1.91, 95% CI 1.19 to 3.06; p=0.007) in the second-line treatment of NSCLC compared with bevacizumab or erlotinib alone. However, no significant difference in OS was observed between the combination and monotherapy groups (HR=0.96, 95% CI 0.83 to 1.11; p=0.573). A subgroup analysis has shown that the greatest PFS benefit was associated with an age of <65 years(HR=0.74, 95% CI 0.57 to 0.96; p=0.026), Asian/Pacific Islander ethnicity (HR=0.23, 95% CI 0.10 to 0.54; p=0.001), Eastern Cooperative Oncology Group performance status (ECOG PS) 1 (HR=0.82, 95% CI 0.68 to 0.98; p=0.033), stage IIIB or IV disease (HR=0.68, 95% CI 0.57 to 0.82; p=0.000) and no history of smoking (HR=0.48, 95% CI 0.32 to 0.71; p=0.000). The incidence of grade 3/4 adverse events such as rash and diarrhoea was higher in the combination group than in the monotherapy group.
  
  
  
  The addition of bevacizumab to erlotinib can significantly improve PFS and the ORR in the second-line treatment of NSCLC with an acceptable and manageable risk of rash and diarrhoea. Further well-conducted, large-scale trials are needed to validate these findings.
authors.affiliation: Department of Respiratory Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Chest Surgery, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Mao
authors.affiliation: Department of Respiratory Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Cai
authors.affiliation: Department of Respiratory Medicine, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D005076:Exanthema / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D008875:Middle Aged; D044468:Native Hawaiian or Pacific Islander; D009367:Neoplasm Staging; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D000074322:Antineoplastic Agents, Immunological; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride
keywords: bevacizumab; erlotinib; meta-analysis; non-small cell lung cancer