title: PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.
abstract: OBJECTIVE
  In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data.
  
  
  METHODS
  In all, 939 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m(2) on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498).
  
  
  RESULTS
  The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients.
  
  
  CONCLUSIONS
  Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.
authors.affiliation: Servicio de Oncología Médica, University Hospital Virgen del Rocío, Seville, Spain. lpazares@hotmail.com
authors.forename: Luis G
authors.initials: LG
authors.lastname: Paz-Ares
authors.forename: Filippo
authors.initials: F
authors.lastname: de Marinis
authors.forename: Mircea
authors.initials: M
authors.lastname: Dediu
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pujol
authors.forename: Paolo
authors.initials: P
authors.lastname: Bidoli
authors.forename: Olivier
authors.initials: O
authors.lastname: Molinier
authors.forename: Tarini Prasad
authors.initials: TP
authors.lastname: Sahoo
authors.forename: Eckart
authors.initials: E
authors.lastname: Laack
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.forename: Jesús
authors.initials: J
authors.lastname: Corral
authors.forename: Symantha
authors.initials: S
authors.lastname: Melemed
authors.forename: William
authors.initials: W
authors.lastname: John
authors.forename: Nadia
authors.initials: N
authors.lastname: Chouaki
authors.forename: Annamaria H
authors.initials: AH
authors.lastname: Zimmermann
authors.forename: Carla
authors.initials: C
authors.lastname: Visseren-Grul
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin