Erlotinib and bevacizumab versus cisplatin, gemcitabine and bevacizumab in unselected nonsquamous nonsmall cell lung cancer

Eur Respir J. 2015 Jul;46(1):219-29. doi: 10.1183/09031936.00229014. Epub 2015 Mar 18.

Abstract

Erlotinib with bevacizumab showed promising activity in recurrent nonsquamous (NS) nonsmall cell lung cancer (NSCLC). The INNOVATIONS study was designed to assess in first-line treatment of unselected cisplatin-eligible patients this combination compared to cisplatin, gemcitabine and bevacizumab. Stage IIIB/IV patients with NS-NSCLC were randomised on erlotinib (150 mg daily) and bevacizumab (15 mg·kg(-1) on day 1, every 3 weeks) (EB) until progression, or cisplatin (80 mg·m(-2) on day 1, every 3 weeks) and gemcitabine (1250 mg·m(-2) on days 1 and 8, every 3 weeks) up to six cycles and bevacizumab (15 mg·kg(-1) on day 1, every 3 weeks) (PGB) until progression. 224 patients were randomised (EB n=111, PGB n=113). The response rate (12% versus 36%; p<0.0001), progression-free survival (median 3.5 versus 6.9 months; hazard ratio (HR) 1.85, 95% CI 1.39-2.45; p<0.0001) and overall survival (median 12.6 versus 17.8 months; HR 1.41, 95% CI 1.01-1.97; p=0.04) clearly favoured PGB. In patients with epidermal growth factor receptor mutations (n=32), response rate, progression-free survival and overall survival were not superior with EB. Platinum-based combination chemotherapy remains the standard of care in first-line treatment of unselected NS-NSCLC. Molecular targeted approaches strongly mandate appropriate testing and patient selection.

Trial registration: ClinicalTrials.gov NCT00536640.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cisplatin / administration & dosage*
  • DNA Mutational Analysis
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Disease Progression
  • Disease-Free Survival
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / administration & dosage*
  • Female
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Mutation
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • Deoxycytidine
  • Bevacizumab
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Cisplatin
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00536640
  • EudraCT/2006-004865-32