A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study

David Bender, Michael W. Sill, Heather A. Lankes, Henry D. Reyes, Christopher J. Darus, James E. Delmore, Jacob Rotmensch, Heidi J. Gray, Robert S. Mannel, Jeanne Schilder, Mark I. Hunter, Carolyn K. McCourt, Megan I. Samuelson, Kimberly K. Leslie

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Purpose Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. Patients and methods Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤ 2 (≤ 1 if two prior cytotoxic regimens given). Cediranib 30 mg orally daily for a 28 day cycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). Results Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. Conclusion Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity.

Original languageEnglish
Pages (from-to)507-512
Number of pages6
JournalGynecologic Oncology
Volume138
Issue number3
DOIs
StatePublished - Sep 1 2015

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Endometrial Neoplasms
Disease-Free Survival
Microvessels
Therapeutics
Female Genital Diseases
Fibroblast Growth Factor Receptors
Neoplasms
Platelet-Derived Growth Factor
cediranib
Hysterectomy
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Disease Progression
Biomarkers
Radiation
Drug Therapy
Survival

Keywords

  • Angiogenesis
  • Fibroblast growth factor receptor
  • Platelet derived growth factor receptor
  • Targeted therapy
  • Tyrosine kinase inhibitor
  • Vascular endothelial growth factor receptor

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer : An NRG Oncology/Gynecologic Oncology Group study. / Bender, David; Sill, Michael W.; Lankes, Heather A.; Reyes, Henry D.; Darus, Christopher J.; Delmore, James E.; Rotmensch, Jacob; Gray, Heidi J.; Mannel, Robert S.; Schilder, Jeanne; Hunter, Mark I.; McCourt, Carolyn K.; Samuelson, Megan I.; Leslie, Kimberly K.

In: Gynecologic Oncology, Vol. 138, No. 3, 01.09.2015, p. 507-512.

Research output: Contribution to journalArticle

Bender, D, Sill, MW, Lankes, HA, Reyes, HD, Darus, CJ, Delmore, JE, Rotmensch, J, Gray, HJ, Mannel, RS, Schilder, J, Hunter, MI, McCourt, CK, Samuelson, MI & Leslie, KK 2015, 'A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study', Gynecologic Oncology, vol. 138, no. 3, pp. 507-512. https://doi.org/10.1016/j.ygyno.2015.07.018
Bender, David ; Sill, Michael W. ; Lankes, Heather A. ; Reyes, Henry D. ; Darus, Christopher J. ; Delmore, James E. ; Rotmensch, Jacob ; Gray, Heidi J. ; Mannel, Robert S. ; Schilder, Jeanne ; Hunter, Mark I. ; McCourt, Carolyn K. ; Samuelson, Megan I. ; Leslie, Kimberly K. / A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer : An NRG Oncology/Gynecologic Oncology Group study. In: Gynecologic Oncology. 2015 ; Vol. 138, No. 3. pp. 507-512.
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abstract = "Purpose Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. Patients and methods Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤ 2 (≤ 1 if two prior cytotoxic regimens given). Cediranib 30 mg orally daily for a 28 day cycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). Results Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52{\%} of patients had received prior radiation, and 73{\%} of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5{\%}. Fourteen patients (29{\%}) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. Conclusion Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity.",
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T1 - A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer

T2 - An NRG Oncology/Gynecologic Oncology Group study

AU - Bender, David

AU - Sill, Michael W.

AU - Lankes, Heather A.

AU - Reyes, Henry D.

AU - Darus, Christopher J.

AU - Delmore, James E.

AU - Rotmensch, Jacob

AU - Gray, Heidi J.

AU - Mannel, Robert S.

AU - Schilder, Jeanne

AU - Hunter, Mark I.

AU - McCourt, Carolyn K.

AU - Samuelson, Megan I.

AU - Leslie, Kimberly K.

PY - 2015/9/1

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N2 - Purpose Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. Patients and methods Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤ 2 (≤ 1 if two prior cytotoxic regimens given). Cediranib 30 mg orally daily for a 28 day cycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). Results Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. Conclusion Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity.

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KW - Fibroblast growth factor receptor

KW - Platelet derived growth factor receptor

KW - Targeted therapy

KW - Tyrosine kinase inhibitor

KW - Vascular endothelial growth factor receptor

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