title: Meta-analysis examining impact of age on overall survival with pemetrexed for the treatment of advanced non-squamous non-small cell lung cancer.
abstract: In clinical practice, elderly patients are often undertreated relative to younger patients. This meta-analysis was designed to determine whether older patients with non-squamous non-small cell lung cancer (NSCLC) could derive an overall survival (OS) benefit from pemetrexed treatment comparable to that experienced by younger patients in the first-line, second-line, or maintenance settings.
  
  
  
  Data from 2671 patients with non-squamous NSCLC participating in four pemetrexed phase III studies were included in a meta-analysis using a random-effects model. Studies included were: JMEI (second-line pemetrexed, N=399); JMDB (first-line pemetrexed/cisplatin, N=1252); JMEN (pemetrexed maintenance after non-pemetrexed/platinum doublet, N=481); and PARAMOUNT (pemetrexed maintenance after first-line pemetrexed/cisplatin, N=539). Patients were predominantly Eastern Cooperative Oncology Group performance status (PS) 0/1. The ratio of OS hazard ratio (HR) (pemetrexed versus control) for younger patients over that for older patients within each study was used as the measure of the differential effect of pemetrexed. Data were examined using age cutoffs of 65 and 70 years.
  
  
  
  Among the four studies, 32% of patients were aged ≥65 years and 14% were aged ≥70 years. The test of heterogeneity among studies was non-significant for subgroups defined by age 65 (P=0.083) and age 70 (P=0.848). The pooled ratio of the OS HR (pemetrexed versus control) in patients <65years to that in patients ≥65 years was 0.92 (95% confidence intervals [CI] 0.67-1.25). Similar results were seen for the analysis using the age 70 years cut-off (0.80 [95% CI 0.62-1.04]).
  
  
  
  In patients with non-squamous NSCLC with good PS, the effect of pemetrexed on OS was not found to be different in younger and older patients undergoing treatment in the first-line, second-line, or maintenance settings.
authors.affiliation: Doce de Octubre University Hospital & Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. Electronic address: lpazaresr@seom.org.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Paz-Ares
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Institutul Oncologic Chiricuta and UMF Cluj-Napoca, Romania.
authors.forename: Tudor
authors.initials: T
authors.lastname: Ciuleanu
authors.affiliation: University of Colorado Cancer Center, Aurora, CO, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bunn
authors.affiliation: Eli Lilly and Company, Madrid, Spain.
authors.forename: Belen San
authors.initials: BS
authors.lastname: Antonio
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Denne
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Iturria
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: William
authors.initials: W
authors.lastname: John
authors.affiliation: University of Torino, Department of Oncology at San Luigi Hospital, Orbassano Torino, Italy.
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D000068437:Pemetrexed / Q000627:therapeutic use*; D010984:Platinum / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068437:Pemetrexed; D010984:Platinum; D002945:Cisplatin
keywords: Advanced non-small cell lung cancer; Elderly; Meta-analysis; Overall survival; Pemetrexed