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.
BACKGROUND
Both bevacizumab and erlotinib have clinical activity in non-small-cell lung cancer (NSCLC). Preclinical data suggest synergistic activity.


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.
Dingemans
A-M C
AC
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.
de Langen
A J
AJ
Departments of Pulmonary Diseases.
van den Boogaart
V
V
Department of Pulmonary Diseases, Maastricht University Medical Center, Maastricht; GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht.
Marcus
J T
JT
Physics and Medical Technology, VU University Medical Center, Amsterdam.
Backes
W H
WH
Department of Radiology, Maastricht University Medical Center, Maastricht.
Scholtens
H T G M
HTGM
Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen.
van Tinteren
H
H
Department of Medical Statistics, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam.
Hoekstra
O S
OS
Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam.
Pruim
J
J
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen.
Brans
B
B
GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht;; Department of Nuclear Medicine, Maastricht University Medical Center, Maastricht.
Thunnissen
F B
FB
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Smit
E F
EF
Departments of Pulmonary Diseases.
Groen
H J M
HJM
Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000008:administration & dosage; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins