Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: A Gynecologic Oncology Group study

Edwin A. Alvarez, William E. Brady, Joan L. Walker, Jacob Rotmensch, Xun C. Zhou, James E. Kendrick, S. Diane Yamada, Jeanne Schilder, David E. Cohn, Charles R. Harrison, Kathleen N. Moore, Carol Aghajanian

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Abstract

Objective This two-stage phase II study was designed to assess the activity of the combination of temsirolimus and bevacizumab in patients with recurrent or persistent endometrial carcinoma (EMC). Methods Eligible patients had persistent or recurrent EMC after receiving 1-2 prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status ≤ 2. Treatment consisted of bevacizumab 10 mg/kg every other week and temsirolimus 25 mg IV weekly until disease progression or prohibitory toxicity. Primary end points were progression-free survival (PFS) at six months and overall response rate using RECIST criteria. Results Fifty-three patients were enrolled. Forty-nine patients were eligible and evaluable. Median age was 63 years, and prior treatment consisted of one or two regimens in 40 (82%) and 9 (18%), respectively. Twenty (41%) received prior radiation. Adverse events were consistent with those expected with bevacizumab and temsirolimus treatment. Two gastrointestinal-vaginal fistulas, one grade 3 epistaxis, two intestinal perforations and 1 grade 4 thrombosis/embolism were seen. Three patient deaths were possibly treatment related. Twelve patients (24.5%) experienced clinical responses (one complete and 11 partial responses), and 23 patients (46.9%) survived progression free for at least six months. Median progression-free survival (PFS) and overall survival (OS) were 5.6 and 16.9 months, respectively. Conclusion Combination of temsirolimus and bevacizumab is deemed active based on both objective tumor response and PFS at six months in recurrent or persistent EMC. However, this treatment regimen was associated with significant toxicity in this pretreated group. Future study will be guided by strategies to decrease toxicity and increase response rates.

Original languageEnglish
Pages (from-to)22-27
Number of pages6
JournalGynecologic Oncology
Volume129
Issue number1
DOIs
StatePublished - Apr 2013

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Endometrial Neoplasms
Disease-Free Survival
Therapeutics
Vaginal Fistula
Female Genital Diseases
Embolism and Thrombosis
Intestinal Perforation
Epistaxis
Bevacizumab
temsirolimus
Disease Progression
Radiation
Survival
Neoplasms

Keywords

  • Bevacizumab
  • GOG
  • Phase II
  • Recurrent endometrial cancer
  • Temsirolimus

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma : A Gynecologic Oncology Group study. / Alvarez, Edwin A.; Brady, William E.; Walker, Joan L.; Rotmensch, Jacob; Zhou, Xun C.; Kendrick, James E.; Yamada, S. Diane; Schilder, Jeanne; Cohn, David E.; Harrison, Charles R.; Moore, Kathleen N.; Aghajanian, Carol.

In: Gynecologic Oncology, Vol. 129, No. 1, 04.2013, p. 22-27.

Research output: Contribution to journalArticle

Alvarez, EA, Brady, WE, Walker, JL, Rotmensch, J, Zhou, XC, Kendrick, JE, Yamada, SD, Schilder, J, Cohn, DE, Harrison, CR, Moore, KN & Aghajanian, C 2013, 'Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: A Gynecologic Oncology Group study', Gynecologic Oncology, vol. 129, no. 1, pp. 22-27. https://doi.org/10.1016/j.ygyno.2012.12.022
Alvarez, Edwin A. ; Brady, William E. ; Walker, Joan L. ; Rotmensch, Jacob ; Zhou, Xun C. ; Kendrick, James E. ; Yamada, S. Diane ; Schilder, Jeanne ; Cohn, David E. ; Harrison, Charles R. ; Moore, Kathleen N. ; Aghajanian, Carol. / Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma : A Gynecologic Oncology Group study. In: Gynecologic Oncology. 2013 ; Vol. 129, No. 1. pp. 22-27.
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abstract = "Objective This two-stage phase II study was designed to assess the activity of the combination of temsirolimus and bevacizumab in patients with recurrent or persistent endometrial carcinoma (EMC). Methods Eligible patients had persistent or recurrent EMC after receiving 1-2 prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status ≤ 2. Treatment consisted of bevacizumab 10 mg/kg every other week and temsirolimus 25 mg IV weekly until disease progression or prohibitory toxicity. Primary end points were progression-free survival (PFS) at six months and overall response rate using RECIST criteria. Results Fifty-three patients were enrolled. Forty-nine patients were eligible and evaluable. Median age was 63 years, and prior treatment consisted of one or two regimens in 40 (82{\%}) and 9 (18{\%}), respectively. Twenty (41{\%}) received prior radiation. Adverse events were consistent with those expected with bevacizumab and temsirolimus treatment. Two gastrointestinal-vaginal fistulas, one grade 3 epistaxis, two intestinal perforations and 1 grade 4 thrombosis/embolism were seen. Three patient deaths were possibly treatment related. Twelve patients (24.5{\%}) experienced clinical responses (one complete and 11 partial responses), and 23 patients (46.9{\%}) survived progression free for at least six months. Median progression-free survival (PFS) and overall survival (OS) were 5.6 and 16.9 months, respectively. Conclusion Combination of temsirolimus and bevacizumab is deemed active based on both objective tumor response and PFS at six months in recurrent or persistent EMC. However, this treatment regimen was associated with significant toxicity in this pretreated group. Future study will be guided by strategies to decrease toxicity and increase response rates.",
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T1 - Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma

T2 - A Gynecologic Oncology Group study

AU - Alvarez, Edwin A.

AU - Brady, William E.

AU - Walker, Joan L.

AU - Rotmensch, Jacob

AU - Zhou, Xun C.

AU - Kendrick, James E.

AU - Yamada, S. Diane

AU - Schilder, Jeanne

AU - Cohn, David E.

AU - Harrison, Charles R.

AU - Moore, Kathleen N.

AU - Aghajanian, Carol

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N2 - Objective This two-stage phase II study was designed to assess the activity of the combination of temsirolimus and bevacizumab in patients with recurrent or persistent endometrial carcinoma (EMC). Methods Eligible patients had persistent or recurrent EMC after receiving 1-2 prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status ≤ 2. Treatment consisted of bevacizumab 10 mg/kg every other week and temsirolimus 25 mg IV weekly until disease progression or prohibitory toxicity. Primary end points were progression-free survival (PFS) at six months and overall response rate using RECIST criteria. Results Fifty-three patients were enrolled. Forty-nine patients were eligible and evaluable. Median age was 63 years, and prior treatment consisted of one or two regimens in 40 (82%) and 9 (18%), respectively. Twenty (41%) received prior radiation. Adverse events were consistent with those expected with bevacizumab and temsirolimus treatment. Two gastrointestinal-vaginal fistulas, one grade 3 epistaxis, two intestinal perforations and 1 grade 4 thrombosis/embolism were seen. Three patient deaths were possibly treatment related. Twelve patients (24.5%) experienced clinical responses (one complete and 11 partial responses), and 23 patients (46.9%) survived progression free for at least six months. Median progression-free survival (PFS) and overall survival (OS) were 5.6 and 16.9 months, respectively. Conclusion Combination of temsirolimus and bevacizumab is deemed active based on both objective tumor response and PFS at six months in recurrent or persistent EMC. However, this treatment regimen was associated with significant toxicity in this pretreated group. Future study will be guided by strategies to decrease toxicity and increase response rates.

AB - Objective This two-stage phase II study was designed to assess the activity of the combination of temsirolimus and bevacizumab in patients with recurrent or persistent endometrial carcinoma (EMC). Methods Eligible patients had persistent or recurrent EMC after receiving 1-2 prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status ≤ 2. Treatment consisted of bevacizumab 10 mg/kg every other week and temsirolimus 25 mg IV weekly until disease progression or prohibitory toxicity. Primary end points were progression-free survival (PFS) at six months and overall response rate using RECIST criteria. Results Fifty-three patients were enrolled. Forty-nine patients were eligible and evaluable. Median age was 63 years, and prior treatment consisted of one or two regimens in 40 (82%) and 9 (18%), respectively. Twenty (41%) received prior radiation. Adverse events were consistent with those expected with bevacizumab and temsirolimus treatment. Two gastrointestinal-vaginal fistulas, one grade 3 epistaxis, two intestinal perforations and 1 grade 4 thrombosis/embolism were seen. Three patient deaths were possibly treatment related. Twelve patients (24.5%) experienced clinical responses (one complete and 11 partial responses), and 23 patients (46.9%) survived progression free for at least six months. Median progression-free survival (PFS) and overall survival (OS) were 5.6 and 16.9 months, respectively. Conclusion Combination of temsirolimus and bevacizumab is deemed active based on both objective tumor response and PFS at six months in recurrent or persistent EMC. However, this treatment regimen was associated with significant toxicity in this pretreated group. Future study will be guided by strategies to decrease toxicity and increase response rates.

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KW - Recurrent endometrial cancer

KW - Temsirolimus

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