title: Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials.
abstract: OBJECTIVE
  Two phase III trials of advanced NSCLC patients were compared to examine relative efficacy and safety of differing treatment regimens. The JMDB trial investigated first-line pemetrexed-cisplatin (pemetrexed 500mg/m(2) plus cisplatin 75mg/m(2) every 21 days; maximum: 6 cycles). The PARAMOUNT phase III trial compared maintenance pemetrexed versus placebo after patients with nonsquamous NSCLC completed 4 cycles of first-line pemetrexed-cisplatin without disease progression.
  
  
  METHODS
  Overall survival (OS) and progression-free survival (PFS), analyzed by Kaplan-Meier and Cox methods, and toxicity rates were compared between the PARAMOUNT arms and a selected homogeneous population from JMDB: 346 patients with disease and prior treatment characteristics matching the PARAMOUNT population.
  
  
  RESULTS
  Outcomes for the PARAMOUNT placebo arm were similar to the JMDB homogeneous group (median PFS: 5.6 versus 6.2 months, p=0.117, HR=1.16; median OS: 14.0 versus 14.2 months, p=0.979, HR=1.00). The PARAMOUNT maintenance pemetrexed group had statistically superior efficacy compared with the JMDB homogeneous group (median PFS: 7.5 versus 6.2 months, p<0.00001, HR=0.66; median OS: 16.9 versus 14.2 months, p=0.003, HR=0.75). Patients who received pemetrexed maintenance (median 4 cycles, range 1-44) following 4 cycles of pemetrexed-cisplatin exhibited a higher incidence of drug-related serious adverse events compared with JMDB patients (median 6 cycles of pemetrexed-cisplatin) (10.6% versus 2.9%); grade 3/4 fatigue and renal toxicity were also higher in the pemetrexed arm of PARAMOUNT.
  
  
  CONCLUSIONS
  The across-trial comparison of a relevant JMDB study population with the two arms of the PARAMOUNT study supported the efficacy of the pemetrexed continuation maintenance strategy and suggested the results are not influenced by limiting the pemetrexed-cisplatin induction treatment to four cycles. Although longer exposure to pemetrexed-cisplatin or maintenance pemetrexed increased some toxicities, the overall incidence remained low, underscoring the relative safety of these treatment regimens.
authors.affiliation: University of Torino at S. Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: G V
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: S. Giuseppe Moscati Hospital, Avellino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gridelli
authors.affiliation: European Institute of Oncology, Thoracic Oncology Division, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: de Marinis
authors.affiliation: Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Germany.
authors.forename: M
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Institute of Oncology Bucharest, Bucharest, Romania.
authors.forename: M
authors.initials: M
authors.lastname: Dediu
authors.affiliation: Montpellier Academic Hospital, Montpellier, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Pujol
authors.affiliation: Heidelberg University Medical Center, Mannheim, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Manegold
authors.affiliation: Eli Lilly and Company, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: San Antonio
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Peterson
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: W
authors.initials: W
authors.lastname: John
authors.affiliation: Eli Lilly and Company, Suresnes, Hauts de Seine, France.
authors.forename: N
authors.initials: N
authors.lastname: Chouaki
authors.affiliation: Eli Lilly and Company, Houten, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Visseren-Grul
authors.affiliation: Instituto de Biomedicina de Sevilla (University Hospital Virgen del Rocío, CSIC and Seville University), Seville, Spain. Electronic address: lpazares@hotmail.com.
authors.forename: L G
authors.initials: LG
authors.lastname: Paz-Ares
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin
keywords: Carcinoma; Cisplatin; Induction chemotherapy; Maintenance chemotherapy; Non-small cell lung; Nonsquamous; Pemetrexed; Phase III clinical trial