title: A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. Electronic address: ddizon@partners.org.
authors.forename: Don S
authors.initials: DS
authors.lastname: Dizon
authors.affiliation: NRG Oncology/Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: msill@gogstats.org.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.affiliation: Indiana University Medical Center, Indianapolis, IN, USA. Electronic address: jschilde@iupui.edu.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Schilder
authors.affiliation: Women's Cancer Care of Seattle, University of Washington, Seattle, WA, USA. Electronic address: kathryn.mcgonigle@nwhsea.org.
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: McGonigle
authors.affiliation: St. Francis Hospital and Medical Center, Hartford, CT, USA. Electronic address: zrahman@stfranciscare.org.
authors.forename: Zia
authors.initials: Z
authors.lastname: Rahman
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: David.Miller@utsouthwestern.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Miller
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mutchd@wudosis.wustl.edu.
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.affiliation: University of Iowa Hospital and Clinics, Iowa City, IA, USA. Electronic address: kimberly-leslie@uiowa.edu.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C530716:nintedanib
keywords: Angiogenesis inhibitor; Clinical trial; Endometrial cancer