title: The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies.
abstract: BACKGROUND
  Recent studies of pemetrexed have identified a predictive role for non-small cell lung cancer (NSCLC) histology. We further reviewed the differential efficacy of pemetrexed according to histology in two large, phase III NSCLC trials.
  
  
  METHODS
  One study tested pemetrexed versus docetaxel in previously treated patients (n = 571) and the other tested cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (n = 1,725) with advanced NSCLC. Cox proportional hazard models were used to test for covariate-adjusted treatment-by-histology interactions (THIs) for overall survival (OS) and progression-free survival (PFS). For each histologic subgroup, the Kaplan-Meier method was used to estimate unadjusted within-arm medians, and Cox models were used to estimate covariate-adjusted between-arm hazard ratios (HRs).
  
  
  RESULTS
  In both studies, treatment arms were well balanced for histology. THIs were statistically significant (p < .005) for both OS and PFS. Nonsquamous patients treated with pemetrexed-based therapy experienced longer survival than the comparators (HR, 0.78 and 0.84, respectively), whereas squamous patients had shorter survival (HR, 1.56 and 1.23, respectively). Whereas the efficacy of pemetrexed regimens differed according to histology, it did not differ for docetaxel or for cisplatin plus gemcitabine. Pemetrexed was well tolerated across histologic groups.
  
  
  CONCLUSIONS
  The consistency of these results across studies confirms the predictive effect of histology for pemetrexed and the survival advantage for pemetrexed in patients with nonsquamous histology. These analyses suggest pemetrexed should not be recommended for the treatment of squamous cell carcinoma, but, because of efficacy and safety advantages, pemetrexed may be preferable to other agents for treatment of patients with nonsquamous NSCLC.
authors.affiliation: Thoracic Oncology Unit, University of Turin, San Luigi Hospital, Orbassano (Torino), Italy. giorgio.scagliotti@unito.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scagliotti
authors.forename: Nasser
authors.initials: N
authors.lastname: Hanna
authors.forename: Frank
authors.initials: F
authors.lastname: Fossella
authors.forename: Katherine
authors.initials: K
authors.lastname: Sugarman
authors.forename: Johannes
authors.initials: J
authors.lastname: Blatter
authors.forename: Patrick
authors.initials: P
authors.lastname: Peterson
authors.forename: Lorinda
authors.initials: L
authors.lastname: Simms
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D000077143:Docetaxel; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine