Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma.
BACKGROUND
To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy.


METHODS
In this two-arm, open-label, phase II study patients were stratified according to their epidermal growth factor receptor (EGFR) gene amplification status. Cetuximab was administered intravenously at a dose of 400 mg/m(2) on week 1 followed by weekly dose of 250 mg/m(2). The primary end point for this study was the response rate in both study arms separately.


RESULTS
Fifty-five eligible patients (28 with and 27 without EGFR amplification) tolerated cetuximab well. Three patients (5.5%) had a partial response and 16 patients (29.6%) had stable disease. The median time to progression was 1.9 months [95% confidence interval (CI) 1.6-2.2 months]. Whereas the progression-free survival (PFS) was <6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of >9 months. Median overall survival was 5.0 months (95% CI 4.2-5.9 months). No significant correlation was found between response, survival and EGFR amplification.


CONCLUSIONS
Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.
Neyns
B
B
Department of Medical Oncology, UZ Brussel, Brussels. Electronic address: bart.neyns@uzbrussel.be.
Sadones
J
J
Department of Medical Oncology, UZ Brussel, Brussels.
Joosens
E
E
Department of Medical Oncology, ZNA Middelheim, Antwerp.
Bouttens
F
F
Department of Radiation therapy, AZ St Lucas, Ghent.
Verbeke
L
L
Department of Radiation therapy, OLV Aalst, Aalst.
Baurain
J-F
JF
Department of Medical Oncology, Cliniques Universitaires St Luc, Brussels.
D'Hondt
L
L
Department of Medical Oncology, Centre Hospitalier Notre-Dame et Reine Fabiola, Charleroi.
Strauven
T
T
Department of Neurology, Sint-Augustinus, Antwerp.
Chaskis
C
C
Department of Neurosurgery.
In't Veld
P
P
Department of Experimental pathology.
Michotte
A
A
Department of Neurology; Department of Neuropathology, UZ Brussel, Brussels, Belgium.
De Greve
J
J
Department of Medical Oncology, UZ Brussel, Brussels.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068818:Cetuximab; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab