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

J Clin Oncol. 2007 Feb 20;25(6):675-81. doi: 10.1200/JCO.2006.07.0649.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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