title: A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse.
abstract: Farletuzumab is a humanized monoclonal antibody that binds to folate receptor-α, which is highly expressed in ovarian carcinoma and largely absent from normal tissue. Farletuzumab was investigated in a double-blind, randomized phase III study in platinum-sensitive ovarian cancer.
  
  
  
  Eligible patients had first recurrent ovarian cancer 6-24 months following completion of platinum-taxane chemotherapy. All patients received carboplatin plus paclitaxel or docetaxel (for six cycles combined with randomly assigned test products in a 1:1:1 ratio: farletuzumab 1.25 mg/kg, farletuzumab 2.5 mg/kg, or placebo). The single-agent test product was continued weekly until disease progression. The primary end point was progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors. Additional analyses not outlined in the original protocol were prespecified in the final statistical analysis plan, including a subgroup analysis by baseline CA-125 and farletuzumab exposure levels.
  
  
  
  A total of 1,100 women were randomly assigned to treatment dose or placebo. PFS from the primary analysis was 9.0, 9.5, and 9.7 months for the placebo, farletuzumab 1.25 mg/kg, and farletuzumab 2.5 mg/kg groups, respectively. Neither farletuzumab group was statistically different from the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.81 to 1.21] and 0.86 [95% CI, 0.70 to 1.06] for farletuzumab 1.25 mg/kg and 2.5 mg/kg group v placebo, respectively). In the prespecified subgroup, baseline CA-125 levels not more than three times the upper limit of normal (ULN) correlated with longer PFS (HR, 0.49; P = .0028) and overall survival (OS) (HR, 0.44; P = .0108) for farletuzumab 2.5 mg/kg versus placebo. Subgroup analysis of farletuzumab exposure above the median, regardless of dose, showed significantly better PFS versus placebo. The most common adverse events were those associated with chemotherapy.
  
  
  
  Neither farletuzumab dose met the study's primary PFS end point. Prespecified subgroup analyses demonstrated that patients with CA-125 levels not more than three times the ULN and patients with higher farletuzumab exposure showed superior PFS and OS compared with placebo.
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH. ignace.vergote@uzleuven.be.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Deborah
authors.initials: D
authors.lastname: Armstrong
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Michael
authors.initials: M
authors.lastname: Teneriello
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Charles
authors.initials: C
authors.lastname: Schweizer
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Weil
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ochiai
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Christopher
authors.initials: C
authors.lastname: Poole
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Shannessy
authors.affiliation: Ignace Vergote, University Hospitals Leuven, Leuven, Belgium; Deborah Armstrong, Johns Hopkins University, Baltimore, MD; Giovanni Scambia, Policlinico Universitario "A. Gemelli", Rome, Italy; Michael Teneriello, US Oncology, The Woodlands, TX; Jalid Sehouli, Charité - Universitätsmedizin Berlin, Berlin, Germany; Charles Schweizer, Susan C. Weil, Wenquan Wang, and Daniel O'Shannessy, Morphotek, Exton, PA; Aristotelis Bamias, Alexandra Hospital, Athens, Greece; Keiichi Fujiwara, Saitama Medical University International Medical Center, Hidaka-City, Saitama; and Kazunori Ochiai, Jikei University School of Medicine, Minato-Ku, Tokyo, Japan; Christopher Poole, University Hospital Coventry, Coventry, United Kingdom; Vera Gorbunova, Russian Oncology Research Center, Moscow, Russia; and Thomas J. Herzog, University of Cincinnati, Cincinnati, OH.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Herzog
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000009:adverse effects; D018394:CA-125 Antigen / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001952:Bridged-Ring Compounds; D018394:CA-125 Antigen; D043823:Taxoids; C080625:taxane; C527484:farletuzumab; D016190:Carboplatin