title: Open-label phase II study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer.
abstract: OBJECTIVE
  To determine the prostate-specific antigen (PSA) 50% decline rate within 24 weeks of starting treatment with single-agent pertuzumab in castrate patients with hormone-refractory prostate cancer (HRPC).
  
  
  METHODS
  Two independent Simon's two-stage designs were used to evaluate two doses of pertuzumab administered intravenously once every 3 weeks. An interim analysis of the first 23 assessable patients in the first cohort treated at 420 mg (loading dose of 840 mg) allowed termination of additional enrollment if three patients had a 50% decline in PSA after all patients had completed at least three cycles of therapy or withdrew due to insufficient therapeutic response, death, or study-related toxicity before completing three cycles. A second cohort of patients treated at 1,050 mg could be enrolled with the same design, and if more than three patients had a 50% decline in PSA, 27 more patients would be treated at 1,050 mg.
  
  
  RESULTS
  Sixty-eight castrate, chemotherapy-naive men with HRPC were enrolled. A total of 35 patients were treated at 420 mg; no PSA declines 50% were observed at the interim analysis and recruitment was stopped. A total of 33 patients were then treated at 1,050 mg, and no PSA declines 50% were observed at the interim analysis. Pertuzumab was well tolerated.
  
  
  CONCLUSIONS
  Pertuzumab has no clinically significant single-agent activity in castrate patients with HRPC at either of the tested dose levels. This may reflect the continued presence of significant levels of intraprostatic androgen driving androgen receptor signaling.
authors.affiliation: Drug Development Unit and Department of Academic Urology, Royal Marsden Hospital, Centre for Cancer Therapeutics, Institute for Cancer Research, Surrey, United Kingdom. jdebono@icr.ac.uk
authors.forename: Johann Sebastian
authors.initials: JS
authors.lastname: de Bono
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Droz
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Aude
authors.initials: A
authors.lastname: Flechon
authors.forename: Cora
authors.initials: C
authors.lastname: Sternberg
authors.forename: Chris
authors.initials: C
authors.lastname: Parker
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zugmaier
authors.forename: Veronica
authors.initials: V
authors.lastname: Hersberger-Gimenez
authors.forename: Louise
authors.initials: L
authors.lastname: Cockey
authors.forename: Malcolm
authors.initials: M
authors.lastname: Mason
authors.forename: John
authors.initials: J
authors.lastname: Graham
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D017430:Prostate-Specific Antigen; C485206:pertuzumab