Don S Dizon1, Michael W Sill2, Jeanne M Schilder3, Kathryn F McGonigle4, Zia Rahman5, David S Miller6, David G Mutch7, Kimberly K Leslie8. 1. Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. Electronic address: ddizon@partners.org. 2. NRG Oncology/Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: msill@gogstats.org. 3. Indiana University Medical Center, Indianapolis, IN, USA. Electronic address: jschilde@iupui.edu. 4. Women's Cancer Care of Seattle, University of Washington, Seattle, WA, USA. Electronic address: kathryn.mcgonigle@nwhsea.org. 5. St. Francis Hospital and Medical Center, Hartford, CT, USA. Electronic address: zrahman@stfranciscare.org. 6. University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: David.Miller@utsouthwestern.edu. 7. Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mutchd@wudosis.wustl.edu. 8. University of Iowa Hospital and Clinics, Iowa City, IA, USA. Electronic address: kimberly-leslie@uiowa.edu.
Abstract
INTRODUCTION: Patients presenting with advanced, recurrent, or metastatic endometrial cancer have limited treatment options. On behalf of the Gynecologic Oncology Group, we conducted this phase II trial of nintedanib (BIBF 1120), a potent small molecule triple receptor tyrosine kinase inhibitor of PDGFR α and β, FGFR 1/3, and VEGFR 1-3, in this population. OBJECTIVES: The primary objectives were to estimate event-free survival (EFS) at 6 months and the proportion of patients who have an objective tumor response. In addition, we sought to determine the nature and degree of toxicity. Secondary objectives were to estimate progression-free and overall survival. METHODS: This was a two-stage, single-arm phase II study. Eligible patients were treated with single-agent nintedanib at a dose of 200mg twice daily. RESULTS: Of 37 patients enrolled, 32 were eligible. There were zero complete and three partial responses for an overall response rate of 9.4% (90% 2-sided CI=2.6-22.5%). Seven patients (21.9%; 90% 2-sided CI=10.7-37.2%) were EFS at 6 months, with one patient continuing on study at the time of this writing. Serious toxicity included the following grade 3 events: gastrointestinal toxicity (5), neutropenia (1), edema (1), hypertension (1), and liver function abnormalities (5). CONCLUSIONS: Nintedanib lacked sufficient activity as a single agent to warrant enrollment to second stage. However, preclinical data indicate it may be synergistic with paclitaxel in a population of patients enriched for specific p53 mutations that result in loss of function. Subsequent studies may evaluate this agent in combination with paclitaxel.
INTRODUCTION:Patients presenting with advanced, recurrent, or metastatic endometrial cancer have limited treatment options. On behalf of the Gynecologic Oncology Group, we conducted this phase II trial of nintedanib (BIBF 1120), a potent small molecule triple receptor tyrosine kinase inhibitor of PDGFR α and β, FGFR 1/3, and VEGFR 1-3, in this population. OBJECTIVES: The primary objectives were to estimate event-free survival (EFS) at 6 months and the proportion of patients who have an objective tumor response. In addition, we sought to determine the nature and degree of toxicity. Secondary objectives were to estimate progression-free and overall survival. METHODS: This was a two-stage, single-arm phase II study. Eligible patients were treated with single-agent nintedanib at a dose of 200mg twice daily. RESULTS: Of 37 patients enrolled, 32 were eligible. There were zero complete and three partial responses for an overall response rate of 9.4% (90% 2-sided CI=2.6-22.5%). Seven patients (21.9%; 90% 2-sided CI=10.7-37.2%) were EFS at 6 months, with one patient continuing on study at the time of this writing. Serious toxicity included the following grade 3 events: gastrointestinal toxicity (5), neutropenia (1), edema (1), hypertension (1), and liver function abnormalities (5). CONCLUSIONS:Nintedanib lacked sufficient activity as a single agent to warrant enrollment to second stage. However, preclinical data indicate it may be synergistic with paclitaxel in a population of patients enriched for specific p53 mutations that result in loss of function. Subsequent studies may evaluate this agent in combination with paclitaxel.
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