A-M C Dingemans1, A J de Langen2, V van den Boogaart3, J T Marcus4, W H Backes5, H T G M Scholtens6, H van Tinteren7, O S Hoekstra8, J Pruim9, B Brans10, F B Thunnissen11, E F Smit2, H J M Groen6. 1. Department of Pulmonary Diseases, Maastricht University Medical Center, Maastricht; GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht;. Electronic address: a.dingemans@mumc.nl. 2. Departments of Pulmonary Diseases. 3. Department of Pulmonary Diseases, Maastricht University Medical Center, Maastricht; GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht. 4. Physics and Medical Technology, VU University Medical Center, Amsterdam. 5. Department of Radiology, Maastricht University Medical Center, Maastricht. 6. Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen. 7. Department of Medical Statistics, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam. 8. Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam. 9. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen. 10. GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht;; Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht. 11. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
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.
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.
Authors: James P B O'Connor; Alan Jackson; Geoff J M Parker; Caleb Roberts; Gordon C Jayson Journal: Nat Rev Clin Oncol Date: 2012-02-14 Impact factor: 66.675
Authors: Michael MacManus; Sarah Everitt; Tanja Schimek-Jasch; X Allen Li; Ursula Nestle; Feng-Ming Spring Kong Journal: Transl Lung Cancer Res Date: 2017-12