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).

Details

Serval ID
serval:BIB_39D6FCC8E3FC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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
Clinical Cancer Research
Author(s)
Cathomas R., Rothermundt C., Klingbiel D., Bubendorf L., Jaggi R., Betticher D.C., Brauchli P., Cotting D., Droege C., Winterhalder R., Siciliano D., Berthold D.R., Pless M., Schiess R., von Moos R., Gillessen S.
Working group(s)
Swiss Group for Clinical Cancer Research SAKK
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
18
Number
21
Pages
6049-6057
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
17/01/2013 8:49
Last modification date
20/08/2019 13:29
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