title: The safety and efficacy of EGFR TKIs monotherapy versus single-agent chemotherapy using third-generation cytotoxics as the first-line treatment for patients with advanced non-small cell lung cancer and poor performance status.
abstract: OBJECTIVE
  To assess the risk/benefit profiles of EGFR TKIs monotherapy using erlotinib or gefitinib in comparison with single-agent chemotherapy using third-generation cytotoxics (gemcitabine, vinorelbine, taxanes) as the first-line treatment for chemonaÏve patients with advanced non-small cell lung cancer (ANSCLC) and poor performance status (PS).
  
  
  METHODS
  A pooled analysis and systematic review was performed using trials identified through MEDLINE, EMBASE, Cochrane Library, and the Clinical-Trials.gov. Data were collected from randomized and non-randomized phase II or III clinical trials of EGFR TKIs monotherapy or single-agent chemotherapy using third-generation cytotoxics published before 3/1/2010, and the pooled estimates for efficacy and safety outcomes of interest were calculated.
  
  
  RESULTS
  Fifteen eligible trials (1425 patients) were selected from 323 studies that initially were identified. In 5 of the selected single-agent chemotherapy studies, the elderly were included together with poor PS patients. Outcomes from these studies still were employed for a thorough analysis. Targeting poor PS patients, we found that the pooled response rate (95% confidence interval) to EGFR TKIs for unselected population was 6% (3-8%), not substantially different from 9% (6-13%) reported by single-agent chemotherapy trials using third-generation cytotoxics. However, EGFR TKIs had better disease control rates with a pooled estimate of 40% (33-47%), significantly higher than 30% (20-41%) of the cytotoxics. Single-agent chemotherapy trials enrolling both elderly and poor PS patients had better results with the pooled response rate and the pooled disease control rate was 13% (11-16%) and 41% (36-46%) respectively. For safety information, despite both treatments were well-tolerated, the toxicity profile of EGFR TKIs was clearly more favorable than that reported by chemotherapy. The severe hematological adverse events related to EGFR TKIs treatment were rare. EGFR TKIs also tended to be more effective in improvement of symptoms or quality-of-life (QOL).
  
  
  CONCLUSIONS
  Although, both of the treatments had low response rates, EGFR TKIs tended to be more effective in control of tumor progression, reduction of therapy-related toxicities, improvement of symptoms or quality-of-life in the first-line treatments of ANSCLC patients with poor PS. Moreover, our data also suggest that the elderly patients without selection carefully according their PS should be separated from this population. Further investigations with valid comparison groups are necessary.
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.forename: Deqiang
authors.initials: D
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhao
authors.forename: Jianqing
authors.initials: J
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D043823:Taxoids; D003841:Deoxycytidine; D014747:Vinblastine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077235:Vinorelbine; D000077156:Gefitinib; D000093542:Gemcitabine