title: Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
abstract: OBJECTIVE
  Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer.
  
  
  METHODS
  Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting.
  
  
  RESULTS
  One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8% in patients who received gemcitabine + pertuzumab compared with 4.6% in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95% CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm.
  
  
  CONCLUSIONS
  Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.
authors.affiliation: Department of Gynecology and Obstetrics, Emory University School of Medicine, Woodruff Memorial Research Bldg, 1639 Pierce Dr 4305, Atlanta, GA 30322, USA. drmakhija@yahoo.com
authors.forename: Sharmila
authors.initials: S
authors.lastname: Makhija
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Amler
authors.forename: Dana
authors.initials: D
authors.lastname: Glenn
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Ueland
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold
authors.forename: Don S
authors.initials: DS
authors.lastname: Dizon
authors.forename: Virginia
authors.initials: V
authors.lastname: Paton
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Thomas
authors.initials: T
authors.lastname: Januario
authors.forename: Kimmie
authors.initials: K
authors.lastname: Ng
authors.forename: Andreas
authors.initials: A
authors.lastname: Strauss
authors.forename: Stephen
authors.initials: S
authors.lastname: Kelsey
authors.forename: Mark X
authors.initials: MX
authors.lastname: Sliwkowski
authors.forename: Ursula
authors.initials: U
authors.lastname: Matulonis
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004311:Double-Blind Method; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D000093542:Gemcitabine; C508053:ERBB2 protein, human; C485206:pertuzumab