First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging

A. -M. C. Dingemans*, Adrianus J. de Langen, V. van den Boogaart, Johannes T. Marcus, W. H. Backes, H. T. G. M. Scholtens, H. van Tinteren, Otto S Hoekstra, Jan Pruim, B. Brans, F. B. Thunnissen, E. F. Smit, H. J. M. Groen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity. Patients and methods: Chemonaive patients with stage IIIb or IV non-squamous NSCLC were treated with bevacizumab 15 mg/kg every 3 weeks and erlotinib 150 mg daily until progression. Primary end point was non-progression rate (NPR) at 6 weeks. Tumor response was measured with computed tomography, 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). KRAS and EGFR mutations were assessed in tumor samples. Results: Forty-seven patients were included. Median follow-up was 15.2 months. NPR at 6 weeks was 75%. Median progression-free survival (PFS) was 3.8 [95% confidence interval (CI) 2.3-5.4] months and median overall survival (OS) was 6.9 (95% CI 5.5-8.4) months. Toxicity was mainly mild. The presence of KRAS (n = 10) or EGFR mutations (n = 5) did not influence outcome. After 3 weeks of treatment, >20% decrease in standard uptake value as measured with positron emission tomography predicted for longer PFS (9.7 versus 2.8 months; P = 0.01) and >40% decrease in K-trans as assessed by DCE-MRI did not predict for longer PFS. Conclusions: First-line treatment with bevacizumab and erlotinib in stage IIIb/IV NSCLC resulted in an NPR of 75%. OS was however disappointing. Early response evaluation with FDG-PET is the best predictive test for PFS.
Original languageEnglish
Pages (from-to)559-566
JournalAnnals of Oncology
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • bevacizumab
  • chemonaive
  • erlotinib
  • imaging
  • NSCLC
  • phase II

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