title: Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089).
abstract: OBJECTIVE
  Maintenance therapy is associated with improved survival in patients with non-small-cell lung cancer (NSCLC), but few studies have compared active agents in this setting. AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment.
  
  
  METHODS
  Patients with advanced nonsquamous NSCLC received first-line bevacizumab 7.5 mg/kg, cisplatin 75 mg/m(2), and pemetrexed 500 mg/m(2) once every 3 weeks for four cycles. Those achieving response or stable disease were randomly assigned at a ratio of 1:1 to maintenance bevacizumab 7.5 mg/kg or bevacizumab 7.5 mg/kg plus pemetrexed 500 mg/m(2) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) after random assignment.
  
  
  RESULTS
  In total, 376 patients received induction treatment, 71.9% achieved disease control, and 67.3% were randomly assigned to maintenance therapy, with 125 and 128 receiving single-agent bevacizumab and bevacizumab plus pemetrexed treatment, respectively. At a median follow-up of 8.1 months, PFS from random assignment was significantly improved in the bevacizumab plus pemetrexed arm (median, 3.7 v 7.4 months; hazard ratio, 0.48; 95% CI, 0.35 to 0.66; P < .001) per a stratified model. The PFS benefit extended across age, performance status, smoking history, and induction response (stable disease v partial response) subgroups. Any grade, grade ≥ 3, and serious adverse events occurred more often with bevacizumab plus pemetrexed maintenance. No new safety signals were observed.
  
  
  CONCLUSIONS
  In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.
authors.affiliation: Aix Marseille University-Assistance Publique Hôpitaux de Marseille and Centre d'Investigation Clinique, Marseille, France. fabrice.barlesi@mail.ap-hm.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherpereel
authors.forename: Achim
authors.initials: A
authors.lastname: Rittmeyer
authors.forename: Antonio
authors.initials: A
authors.lastname: Pazzola
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer Tur
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.forename: Joachim G J V
authors.initials: JG
authors.lastname: Aerts
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.forename: Anders
authors.initials: A
authors.lastname: Vikström
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Wong
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Moreno
authors.forename: Lada
authors.initials: L
authors.lastname: Mitchell
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; 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*; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D002945:Cisplatin