Efficacy and safety of single-agent pertuzumab (rhuMAb 2C4), a human epidermal growth factor receptor dimerization inhibitor, in castration-resistant prostate cancer after progression from taxane-based therapy.

Abstract

PURPOSE:

Pertuzumab represents a new class of targeted anticancer agents, human epidermal growth factor receptor (HER) dimerization inhibitors. The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent pertuzumab in castration-resistant prostate cancer (CRPC) patients who had experienced progression after prior chemotherapy.

PATIENTS AND METHODS:

Patients received pertuzumab every 3 weeks. All castration-resistant patients had experienced progression after at least one taxane-based regimen. Patients received a loading dose of 840 mg pertuzumab (cycle 1) followed by 420 mg for subsequent cycles. The primary end point was overall response and safety. A separate retrospective analysis of actual survival time versus predicted survival time for a patient population with comparable prognostic features was performed.

RESULTS:

Patients were enrolled (N = 42) and treated (n = 41). No patients had complete or partial response (as defined by Response Evaluation Criteria in Solid Tumors Group or 50% decline in prostate-specific antigen). Of 30 efficacy-assessable patients, five had stable disease (SD) for at least 23 weeks; one of five had SD for 36 weeks. Pertuzumab was well tolerated; diarrhea was the most common adverse effect (61.0%, grades 1 to 3). Retrospective analysis of survival using a validated nomogram suggested that survival was prolonged with pertuzumab treatment, compared with historic controls with similar baseline prognostic features.

CONCLUSION:

Pertuzumab was well tolerated and resulted in no objective responses, but several patients had SD more than 23 weeks from a heavily pretreated population. Retrospective analysis suggested prolonged median survival time with pertuzumab compared with historical controls. Thus, inhibition of HER dimerization may have clinical utility in CRPC patients.

• Authors: David B Agus, Christopher J Sweeney, Michael J Morris, David S Mendelson, Douglas G McNeel, Frederick R Ahmann, Jin Wang, Mika K Derynck, Kimmie Ng, Benjamin Lyons, David E Allison, Michael W Kattan, Howard I Scher
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 25 Issue 6 Pg. 675-81 (Feb 20 2007) ISSN: 1527-7755 [Electronic] United States
• PMID: 17308272 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Bridged-Ring Compounds
• Taxoids
• taxane
• Receptor, ErbB-2
• pertuzumab

Topics

• Aged
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Bridged-Ring Compounds (adverse effects, therapeutic use)
• Disease Progression
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Orchiectomy
• Probability
• Prognosis
• Prostatic Neoplasms (drug therapy, mortality, pathology, surgery)
• Receptor, ErbB-2 (administration & dosage, antagonists & inhibitors)
• Risk Assessment
• Single-Blind Method
• Survival Analysis
• Taxoids (adverse effects, therapeutic use)
• Treatment Outcome