title: 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: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Cedars-Sinai Prostate Cancer Center, Los Angeles, CA 90048, USA. David.Agus@cshs.org
authors.forename: David B
authors.initials: DB
authors.lastname: Agus
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.forename: David S
authors.initials: DS
authors.lastname: Mendelson
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McNeel
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Ahmann
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Mika K
authors.initials: MK
authors.lastname: Derynck
authors.forename: Kimmie
authors.initials: K
authors.lastname: Ng
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lyons
authors.forename: David E
authors.initials: DE
authors.lastname: Allison
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001952:Bridged-Ring Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009919:Orchiectomy; D011336:Probability; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D018570:Risk Assessment; D016037:Single-Blind Method; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001952:Bridged-Ring Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C080625:taxane; C485206:pertuzumab