PURPOSE:The epidermal growth factor receptor (EGFR) is overexpressed in the majority of metastatic castration-resistant prostate cancers (mCRPC) and might represent a valid therapeutic target.
The combination of docetaxel and cetuximab, the monoclonal antibody against EGFR, has not been tested in prostate cancer patients. Experimental design: Patients with mCRPC progressing during or within 90 days after at least 12 weeks of docetaxel were included in this phase II trial. Treatment consisted of docetaxel (75mg/m2 q3w or 35mg/m2 d1, 8, 15 q4w) in combination with cetuximab (400mg/m2 d1, then 250mg/m2 weekly). The primary endpoint was progression-free survival (PFS) at 12 weeks defined as absence of PSA, radiographic or clinical progression. Evaluation of known biomarkers of response and resistance to cetuximab (EGFR, PTEN, amphiregulin, epiregulin) was performed.
RESULTS:38 patients were enrolled at 15 Swiss centers. Median age was 68 years and median PSA 212 ng/ml. PFS at 12 weeks was 34% (95%CI 19-52%), PFS at 24 weeks was 20% and median overall survival (OS) was 13.3 months (95%CI 7.3 - 15.4). Seven patients (20%) had a confirmed ≥ 50% and eleven patients (31%) a confirmed ≥ 30% PSA decline. 47% of enrolled patients experienced grade 3 and 8% grade 4 toxicities. A significantly improved PFS was found in patients with overexpression of EGFR and persistent activity of PTEN.
CONCLUSIONS: EGFR inhibition with cetuximab might improve the outcome of patients with mCRPC. A potential correlation between EGFR overexpression, persistent expression of PTEN and EGFR inhibition should be investigated further.
Written by:
Cathomas R, Rothermundt C, Klingbiel D, Bubendorf L, Jaggi R, Betticher DC, Brauchli P, Cotting D, Droege C, Winterhalder R, Siciliano D, Berthold DR, Pless M, Schiess R, von Moos R, Gillessen S. Are you the author?
Medical Oncology, Kantonsspital Graubünden.
Reference: Clin Cancer Res. 2012 Sep 12. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-12-2219
PubMed Abstract
PMID: 22977195
UroToday.com Prostate Cancer Section
