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

Ann Oncol. 2014 May;25(5):1044-52. doi: 10.1093/annonc/mdu098. Epub 2014 Feb 27.


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.

Patients and 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.

Conclusion: 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.

Keywords: bevacizumab; chemotherapy; maintenance; nonsmall-cell lung cancer; nonsquamous; pemetrexed.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cisplatin / administration & dosage
  • Disease-Free Survival
  • Female
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Pemetrexed
  • Proportional Hazards Models
  • Quality of Life
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Glutamates
  • Pemetrexed
  • Bevacizumab
  • Guanine
  • Cisplatin