A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer

An NRG Oncology/Gynecologic Oncology Group Study

Don S. Dizon, Michael W. Sill, Jeanne Schilder, Kathryn F. McGonigle, Zia Rahman, David S. Miller, David G. Mutch, Kimberly K. Leslie

Research output: Contribution to journalArticle

29 Citations (Scopus)

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 200 mg 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.

Original languageEnglish
Pages (from-to)441-445
Number of pages5
JournalGynecologic Oncology
Volume135
Issue number3
DOIs
StatePublished - Dec 1 2014

Fingerprint

Endometrial Neoplasms
Disease-Free Survival
Paclitaxel
Therapeutics
Vascular Endothelial Growth Factor Receptor-3
Vascular Endothelial Growth Factor Receptor-1
Receptor Protein-Tyrosine Kinases
nintedanib
Neutropenia
Population
Edema
Hypertension
Mutation
Liver
Neoplasms

Keywords

  • Angiogenesis inhibitor
  • Clinical trial
  • Endometrial cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer : An NRG Oncology/Gynecologic Oncology Group Study. / Dizon, Don S.; Sill, Michael W.; Schilder, Jeanne; McGonigle, Kathryn F.; Rahman, Zia; Miller, David S.; Mutch, David G.; Leslie, Kimberly K.

In: Gynecologic Oncology, Vol. 135, No. 3, 01.12.2014, p. 441-445.

Research output: Contribution to journalArticle

Dizon, Don S. ; Sill, Michael W. ; Schilder, Jeanne ; McGonigle, Kathryn F. ; Rahman, Zia ; Miller, David S. ; Mutch, David G. ; Leslie, Kimberly K. / A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer : An NRG Oncology/Gynecologic Oncology Group Study. In: Gynecologic Oncology. 2014 ; Vol. 135, No. 3. pp. 441-445.
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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 200 mg 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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T1 - A phase II evaluation of nintedanib (BIBF-1120) in the treatment of recurrent or persistent endometrial cancer

T2 - An NRG Oncology/Gynecologic Oncology Group Study

AU - Dizon, Don S.

AU - Sill, Michael W.

AU - Schilder, Jeanne

AU - McGonigle, Kathryn F.

AU - Rahman, Zia

AU - Miller, David S.

AU - Mutch, David G.

AU - Leslie, Kimberly K.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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 200 mg 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.

AB - 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 200 mg 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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