Publication
Efficacy of cetuximab in metastatic castration-resistant prostate cancer might depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07)
Journal Paper/Review - Sep 12, 2012
Cathomas Richard, Gillessen Sommer Silke, von Moos Roger, Schiess Ralph, Pless Miklos, Berthold Dominik R, Siciliano Daniele, Winterhalder Ralph, Droege Cornelia, Cotting Denise, Brauchli Peter, Betticher Daniel C, Jaggi Rolf, Bubendorf Lukas, Klingbiel Dirk, Rothermundt Christian, Swiss Group for Clinical Cancer Research SAKK
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PubMed
Doi
Citation
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Journal
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Issn Print
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Brief description/objective
PURPOSE
The EGF 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 patients with prostate cancer.
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 (75 mg/m(2) every 3 weeks or 35 mg/m(2) on days 1, 8, 15 every 4 weeks) in combination with cetuximab (400 mg/m(2) on day 1 and then 250 mg/m(2) weekly). The primary endpoint was progression-free survival (PFS) at 12 weeks defined as the absence of prostate-specific antigen (PSA), radiographic, or clinical progression. Evaluation of known biomarkers of response and resistance to cetuximab (EGFR, PTEN, amphiregulin, epiregulin) was conducted.
RESULTS
Thirty-eight patients were enrolled at 15 Swiss centers. Median age was 68 years and median PSA was 212 ng/mL. PFS at 12 weeks was 34% [95% confidence interval (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 11 patients (31%) a confirmed ≥ 30% PSA decline. About 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.