1. 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.
- Author
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Dingemans AC, de Langen AJ, van den Boogaart V, Marcus JT, Backes WH, Scholtens HTGM, van Tinteren H, Hoekstra OS, Pruim J, Brans B, Thunnissen FB, Smit EF, and Groen HJM
- Subjects
- Adult, Aged, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal, Humanized, Bevacizumab, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Drug-Related Side Effects and Adverse Reactions, ErbB Receptors genetics, Erlotinib Hydrochloride, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms mortality, Lung Neoplasms pathology, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Neoplasm Metastasis, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins p21(ras), Quinazolines administration & dosage, Tomography, Emission-Computed, Treatment Outcome, ras Proteins genetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- 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.
- Published
- 2011
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