Ignace Vergote1, Deborah Armstrong2, Giovanni Scambia2, Michael Teneriello2, Jalid Sehouli2, Charles Schweizer2, Susan C Weil2, Aristotelis Bamias2, Keiichi Fujiwara2, Kazunori Ochiai2, Christopher Poole2, Vera Gorbunova2, Wenquan Wang2, Daniel O'Shannessy2, Thomas J Herzog2. 1. 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. 2. 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.
Abstract
PURPOSE: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. PATIENTS AND METHODS: Eligible patients had first recurrent ovarian cancer 6-24 months following completion ofplatinum-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. RESULTS: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. CONCLUSION: 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.
RCT Entities:
PURPOSE: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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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: Kathleen N Moore; Hossein Borghaei; David M O'Malley; Woondong Jeong; Shelly M Seward; Todd M Bauer; Raymond P Perez; Ursula A Matulonis; Kelli L Running; Xiaoyan Zhang; Jose F Ponte; Rodrigo Ruiz-Soto; Michael J Birrer Journal: Cancer Date: 2017-04-25 Impact factor: 6.860
Authors: A Oaknin; R Guarch; P Barretina; D Hardisson; A González-Martín; X Matías-Guiu; A Pérez-Fidalgo; B Vieites; I Romero; J Palacios Journal: Clin Transl Oncol Date: 2017-08-16 Impact factor: 3.405
Authors: Dandan Yu; Ruth Holm; Mariusz Adam Goscinski; Claes G Trope; Jahn M Nesland; Zhenhe Suo Journal: Am J Cancer Res Date: 2016-09-01 Impact factor: 6.166
Authors: Kimberly R Kalli; Matthew S Block; Pashtoon M Kasi; Courtney L Erskine; Timothy J Hobday; Allan Dietz; Douglas Padley; Michael P Gustafson; Barath Shreeder; Danell Puglisi-Knutson; Dan W Visscher; Toni K Mangskau; Glynn Wilson; Keith L Knutson Journal: Clin Cancer Res Date: 2018-03-15 Impact factor: 12.531
Authors: Gururaj Shivange; Karol Urbanek; Piotr Przanowski; Justin S A Perry; James Jones; Robert Haggart; Christina Kostka; Tejal Patki; Edward Stelow; Yuliya Petrova; Danielle Llaneza; Marty Mayo; Kodi S Ravichandran; Charles N Landen; Sanchita Bhatnagar; Jogender Tushir-Singh Journal: Cancer Cell Date: 2018-08-13 Impact factor: 31.743