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HER-2 profiling and targeting in prostate carcinoma
Michael J Morris1, Victor E Reuter, W Kevin Kelly
1Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Background:
The clinical effects of targeting HER-2 in prostate carcinoma are not known. This study explored the feasibility of molecular profiling to determine the correlation between HER-2 expression, hormonal sensitivity, and the antitumor effects of trastuzumab and paclitaxel in patients with prostate carcinoma.
Methods:
Patients with progressive androgen dependent (AD) and androgen independent (AI) prostate carcinoma were eligible to participate in the study. HER-2 expression was assessed on pretreatment tissue specimens, and patients were then assigned to one of four treatment groups: AD HER-2 positive, AD HER-2 negative, AI HER-2 positive, and AI HER-2 negative. They were treated with weekly trastuzumab at a dose of 2 mg/kg (after a 4 mg/kg loading dose) until they experienced disease progression, when weekly paclitaxel at 100 mg/m(2) was added.
Results:
The authors screened 130 patients for HER-2 expression. In total, 23 patients were treated. Six eligible patients had HER-2 positive disease; therefore, only the AI HER-2 negative arm accrued to completion. All patients (100%) experienced disease progression on trastuzumab alone at or before the first 12 weeks of treatment. Fifteen patients received combined therapy: Seven patients (47%) experienced disease progression, 5 patients (33%) had stable disease, and 3 patients (20%) had a decline > or = 50% in prostate specific antigen PSA level or in soft tissue disease. HER-2 overexpression was found in significant proportions only in AI metastatic tissue samples (42% HER-2 positive; 95% confidence interval, 14-60%). In three of nine matched pairs, the AD prostate biopsy was HER-2 negative, and the AI metastatic sample was HER-2 positive.
Conclusions:
Trastuzumab is not effective as a single agent for the treatment of patients with AI HER-2 negative tumors. HER-2 expression varies by clinical state in patients with prostate carcinoma: Accurate HER-2 profiling requires sampling metastatic tissue in patients with metastatic disease. Further development of trastuzumab for the treatment of patients with metastatic prostate carcinoma is not feasible until more reliable and practical methods of sampling metastatic disease are developed to identify patients with HER-2 positive tumors.
Insights
Trastuzumab is ineffective for HER-2 negative prostate cancer. Accurate HER-2 profiling requires metastatic tissue sampling for effective targeted therapy development in advanced prostate carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The role of HER-2 (Human Epidermal growth factor Receptor 2) in prostate carcinoma remains unclear.
- This study investigated the feasibility of molecular profiling to correlate HER-2 expression with hormonal sensitivity and treatment response in prostate cancer patients.
Purpose of the Study:
- To explore the clinical effects of targeting HER-2 in prostate carcinoma.
- To determine the correlation between HER-2 expression, hormonal sensitivity, and the antitumor effects of trastuzumab and paclitaxel.
Main Methods:
- Patients with progressive androgen-dependent (AD) and androgen-independent (AI) prostate carcinoma were enrolled.
- HER-2 expression was assessed on pretreatment tissue. Patients were assigned to treatment groups based on HER-2 status and hormonal sensitivity.
- Treatment involved weekly trastuzumab, with paclitaxel added upon disease progression.
Main Results:
- Out of 130 screened patients, 23 were treated. Only the AI HER-2 negative arm completed due to limited HER-2 positive cases.
- All patients (100%) progressed on trastuzumab monotherapy within 12 weeks.
- HER-2 overexpression was primarily observed in AI metastatic samples (42%).
Conclusions:
- Trastuzumab is not effective as a single agent for HER-2 negative AI prostate tumors.
- HER-2 expression can vary between AD and AI states, necessitating metastatic tissue sampling for accurate profiling.
- Further development of trastuzumab for prostate cancer is contingent on improved methods for identifying HER-2 positive metastatic disease.