title: Afatinib in the treatment of EGFR mutation-positive NSCLC--a network meta-analysis.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is a specific lung cancer subtype characterized by sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs). Two reversible EGFR TKIs (gefitinib, erlotinib) and the irreversible ErbB family blocker afatinib are currently approved for treatment of EGFR mutation-positive NSCLC, but no head-to-head trials have been reported to date. We aimed to assess the relative efficacy of the three drugs by conducting a network meta-analysis (NMA).
  
  
  METHODS
  A systematic literature review was conducted to identify all the available evidence. Outcomes of interest were progression-free survival (PFS) and overall survival. For PFS, results by investigator review were considered as not all trials assessed PFS independently. Results were analyzed using Bayesian methods.
  
  
  RESULTS
  The literature search identified 246 articles that were assessed for eligibility, of which 21 studies were included in the NMA, including eight trials performed in an EGFR mutation-positive population. The estimated PFS HR (95% credible interval, CrI) for afatinib compared with gefitinib was 0.70 (0.40-1.16) and compared with erlotinib was 0.86 (0.50-1.50) in the total population. The estimated probability of being best for afatinib over all other treatments for PFS was 70% versus 27% for erlotinib and 3% for gefitinib; the estimated probability of chemotherapy being the best treatment was 0%. Estimated HR (95% CrI) in patients with common mutations was 0.73 (0.42-1.24) for afatinib compared with erlotinib and 0.60 (0.34-0.99) for afatinib compared with gefitinib. OS findings were not significantly different between treatments.
  
  
  CONCLUSIONS
  In the absence of direct head-to-head trial data comparing efficacy between the three EGFR TKIs, our analysis suggests that afatinib is a viable treatment alternative to erlotinib or gefitinib in terms of PFS. A direct trial-based comparison of the efficacy of these agents is warranted to clarify their relative benefits.
authors.affiliation: Royal Marsden Hospital, London, UK. Electronic address: sanjay.popat@rmh.nhs.uk.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Popat
authors.affiliation: State Key Laboratory of Southern China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: National Taiwan University, Taipei, Taiwan.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Boehringer Ingelheim GmbH, Ingelheim, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Lungershausen
authors.affiliation: Boehringer Ingelheim GmbH, Ingelheim, Germany.
authors.forename: Uz
authors.initials: U
authors.lastname: Stammberger
authors.affiliation: Boehringer Ingelheim GmbH, Ingelheim, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Griebsch
authors.affiliation: IMS Health, London, UK.
authors.forename: Tiago
authors.initials: T
authors.lastname: Fonseca
authors.affiliation: Instituto de Biomedicina de Sevilla - IBIS (University Hospital Virgen del Rocío, US, CSIC), Seville, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
mesh_terms: D000077716:Afatinib; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009154:Mutation; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D066246:ErbB Receptors
keywords: Afatinib; Chemotherapy; Epidermal growth factor receptor (EGFR); Erlotinib; Gefitinib; NSCLC; Tyrosine kinase inhibitor