Lainie P Martin1, Michael Sill2, Mark S Shahin3, Matthew Powell4, Paul DiSilvestro5, Lisa M Landrum6, Stephanie L Gaillard7, Michael J Goodheart8, James Hoffman9, Russell J Schilder10. 1. Dept. of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Electronic address: lainie.martin@fccc.edu. 2. Gynecologic Oncology Group Statistical & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. 3. Dept. of Clinical Gynecologic Oncology, Hanjani Institute for Gynecologic Oncology, Abington Memorial Hospital, Abington, PA 19001, USA. 4. Dept. of OB/GYN, Washington University School of Medicine, St. Louis, MO 63110, USA. 5. Program in Women's Oncology, Women & Infants Hospital/Alpert School of Medicine, Providence, RI 02905, USA. 6. Dept. of OB/GYN, Oklahoma University Health Science Center, Oklahoma City, OK 73104, USA. 7. Dept. of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27710, USA. 8. Dept. of Gynecologic Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. 9. Dept. of Gynecologic Oncology, The Hospital of Central Connecticut, New Britain, CT 06050, USA. 10. Dept. of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Abstract
OBJECTIVE: This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer. PATIENTS AND METHODS: Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of <12 months or a second recurrence, and adequate bone marrow and organ function. Patients received rilotumumab 20mg/kg IV every 14 days until evidence of unacceptable toxicity or disease progression. The study utilized co-dual primary endpoints of tumor response and six-month PFS to assess the efficacy of rilotumumab. Secondary endpoints included the frequency and severity of adverse events and the duration of progression-free and overall survival. RESULTS: Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2-14%), and two women had 6-month PFS (6.5%; 90% CI 1.1-19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event (1), ventricular tachycardia (1), hypotension during infusion (1) and fatigue (1). The study was stopped after the first stage of accrual. CONCLUSION: Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian cancer.
OBJECTIVE: This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer. PATIENTS AND METHODS: Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of <12 months or a second recurrence, and adequate bone marrow and organ function. Patients received rilotumumab 20mg/kg IV every 14 days until evidence of unacceptable toxicity or disease progression. The study utilized co-dual primary endpoints of tumor response and six-month PFS to assess the efficacy of rilotumumab. Secondary endpoints included the frequency and severity of adverse events and the duration of progression-free and overall survival. RESULTS: Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2-14%), and two women had 6-month PFS (6.5%; 90% CI 1.1-19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event (1), ventricular tachycardia (1), hypotension during infusion (1) and fatigue (1). The study was stopped after the first stage of accrual. CONCLUSION:Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian cancer.
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