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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

Dingemans, A. -M. C., de Langen, A. J., van den Boogaart, V., Marcus, J. T., Backes, W. H., Scholtens, H. T. G. M., van Tinteren, H., Hoekstra, O. S., Pruim, J., Brans, B., Thunnissen, F. B., Smit, E. F. & Groen, H. J. M., Mar-2011, In : Annals of Oncology. 22, 3, p. 559-566 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

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
Number of pages8
JournalAnnals of Oncology
Volume22
Issue number3
Publication statusPublished - Mar-2011

    Keywords

  • bevacizumab, chemonaive, erlotinib, imaging, NSCLC, phase II, GROWTH-FACTOR RECEPTOR, POSITRON-EMISSION-TOMOGRAPHY, CISPLATIN PLUS GEMCITABINE, ANTIBODY BEVACIZUMAB, COLORECTAL-CANCER, CHEMOTHERAPY, TRIAL, INHIBITOR, THERAPY, TUMOR

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