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)

• Published in: Clinical cancer research 2012-11, Vol.18 (21), p.6049-6057
• Main Authors: CATHOMAS, Richard, ROTHERMUNDT, Christian, SICILIANO, Daniele, BERTHOLD, Dominik R, PLESS, Miklos, SCHIESS, Ralph, MOOS, Roger Von, GILLESSEN, Silke, KLINGBIEL, Dirk, BUBENDORF, Lukas, JAGGI, Rolf, BETTICHER, Daniel C, BRAUCHLI, Peter, COTTING, Denise, DROEGE, Cornelia, WINTERHALDER, Ralph
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cetuximab; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Orchiectomy; Pharmacology. Drug treatments; Prostate-Specific Antigen - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; PTEN Phosphohydrolase - genetics; Receptor, Epidermal Growth Factor - genetics; Taxoids - administration & dosage; Translational Medical Research; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-12-2219

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. 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. 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. 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.