title: Maintenance bevacizumab-pemetrexed after first-line cisplatin-pemetrexed-bevacizumab for advanced nonsquamous nonsmall-cell lung cancer: updated survival analysis of the AVAPERL (MO22089) randomized phase III trial.
abstract: BACKGROUND
  The randomized, phase III AVAPERL trial evaluated the safety and efficacy of bevacizumab maintenance with or without pemetrexed in nonsquamous nonsmall-cell lung cancer (nsNSCLC). Progression-free survival (PFS) was significantly prolonged with bevacizumab-pemetrexed, but overall survival (OS) data were immature. In this article, we report an independent, updated analysis of survival outcomes in AVAPERL.
  
  
  METHODS
  Patients with advanced nsNSCLC received first-line bevacizumab (7.5 mg/kg), cisplatin (75 mg/m(2)), and pemetrexed (500 mg/m(2)) every 3 weeks (q3w) for four cycles. Nonprogressing patients were randomized to maintenance bevacizumab (7.5 mg/kg) or bevacizumab-pemetrexed (500 mg/m(2)) q3w until progression or consent withdrawal. The primary end point of the trial was PFS; in this independent OS analysis, participating study centers were contacted to collect survival data on patients still alive at the time of the first analysis.
  
  
  RESULTS
  A total of 376 patients received induction treatment. Disease control was confirmed in 71.9% of patients; 253 patients were randomized to maintenance treatment with bevacizumab (n = 125) or bevacizumab-pemetrexed (n = 128). At a median follow-up of 14.8 months, patients allocated to bevacizumab-pemetrexed had significantly improved PFS versus those on bevacizumab when measured from randomization [7.4 versus 3.7 months, hazard ratio (HR), 0.57, 95% confidence interval (CI) 0.44-0.75); P < 0.0001]. OS events occurred in 58% of all patients. OS was numerically longer with bevacizumab-pemetrexed versus bevacizumab when measured from randomization [17.1 versus 13.2 months, HR 0.87 (0.63-1.21); P = 0.29]. Second-line therapy was administered in 77% and 70% of patients in the bevacizumab and bevacizumab-pemetrexed arms, respectively. No new adverse events were reported during this updated analysis.
  
  
  CONCLUSIONS
  In an unselected population of nsNSCLC patients achieving disease control on platinum-based induction therapy, maintenance with bevacizumab-pemetrexed was associated with a nonsignificant increase in OS over bevacizumab alone.
authors.affiliation: Multidisciplinary Oncology and Therapeutic Innovations Department & Centre Investigation Clinique, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, INSERM CIC, Marseille.
authors.forename: F
authors.initials: F
authors.lastname: Barlesi
authors.forename: A
authors.initials: A
authors.lastname: Scherpereel
authors.forename: V
authors.initials: V
authors.lastname: Gorbunova
authors.forename: R
authors.initials: R
authors.lastname: Gervais
authors.forename: A
authors.initials: A
authors.lastname: Vikström
authors.forename: C
authors.initials: C
authors.lastname: Chouaid
authors.forename: A
authors.initials: A
authors.lastname: Chella
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: M J
authors.initials: MJ
authors.lastname: Ahn
authors.forename: M
authors.initials: M
authors.lastname: Reck
authors.forename: A
authors.initials: A
authors.lastname: Pazzola
authors.forename: H T
authors.initials: HT
authors.lastname: Kim
authors.forename: J G
authors.initials: JG
authors.lastname: Aerts
authors.forename: C
authors.initials: C
authors.lastname: Morando
authors.forename: A
authors.initials: A
authors.lastname: Loundou
authors.forename: H J M
authors.initials: HJ
authors.lastname: Groen
authors.forename: A
authors.initials: A
authors.lastname: Rittmeyer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D016016:Proportional Hazards Models; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D002945:Cisplatin
keywords: bevacizumab; chemotherapy; maintenance; nonsmall-cell lung cancer; nonsquamous; pemetrexed