A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer

A Gynecologic Oncology Group study

Kimberly K. Leslie, Michael W. Sill, Edgar Fischer, Kathleen M. Darcy, Robert S. Mannel, Krishnansu S. Tewari, Parviz Hanjani, Jason A. Wilken, Andre T. Baron, Andrew K. Godwin, Russell J. Schilder, Meenakshi Singh, Nita Jane Maihle

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Abstract

Background A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. Methods Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500 mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. Results Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥ 6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. Conclusions This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.

Original languageEnglish (US)
Pages (from-to)486-494
Number of pages9
JournalGynecologic Oncology
Volume129
Issue number3
DOIs
StatePublished - Jun 1 2013

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Endometrial Neoplasms
Epidermal Growth Factor Receptor
Extracellular Signal-Regulated MAP Kinases
Disease-Free Survival
Estrogen Receptors
Survival
Serum
Therapeutics
Neoplasms
Tumor Biomarkers
gefitinib
Safety
Mutation
progesterone receptor A

Keywords

  • Endometrial cancer
  • Epidermal growth factor receptor (EGFR)
  • Estrogen receptor
  • Gefitinib
  • Progesterone receptor
  • Soluble EGFR

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Leslie, K. K., Sill, M. W., Fischer, E., Darcy, K. M., Mannel, R. S., Tewari, K. S., ... Maihle, N. J. (2013). A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study. Gynecologic Oncology, 129(3), 486-494. https://doi.org/10.1016/j.ygyno.2013.02.019

A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer : A Gynecologic Oncology Group study. / Leslie, Kimberly K.; Sill, Michael W.; Fischer, Edgar; Darcy, Kathleen M.; Mannel, Robert S.; Tewari, Krishnansu S.; Hanjani, Parviz; Wilken, Jason A.; Baron, Andre T.; Godwin, Andrew K.; Schilder, Russell J.; Singh, Meenakshi; Maihle, Nita Jane.

In: Gynecologic Oncology, Vol. 129, No. 3, 01.06.2013, p. 486-494.

Research output: Contribution to journalArticle

Leslie, KK, Sill, MW, Fischer, E, Darcy, KM, Mannel, RS, Tewari, KS, Hanjani, P, Wilken, JA, Baron, AT, Godwin, AK, Schilder, RJ, Singh, M & Maihle, NJ 2013, 'A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study', Gynecologic Oncology, vol. 129, no. 3, pp. 486-494. https://doi.org/10.1016/j.ygyno.2013.02.019
Leslie, Kimberly K. ; Sill, Michael W. ; Fischer, Edgar ; Darcy, Kathleen M. ; Mannel, Robert S. ; Tewari, Krishnansu S. ; Hanjani, Parviz ; Wilken, Jason A. ; Baron, Andre T. ; Godwin, Andrew K. ; Schilder, Russell J. ; Singh, Meenakshi ; Maihle, Nita Jane. / A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer : A Gynecologic Oncology Group study. In: Gynecologic Oncology. 2013 ; Vol. 129, No. 3. pp. 486-494.
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abstract = "Background A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. Methods Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500 mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. Results Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥ 6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. Conclusions This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.",
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AU - Fischer, Edgar

AU - Darcy, Kathleen M.

AU - Mannel, Robert S.

AU - Tewari, Krishnansu S.

AU - Hanjani, Parviz

AU - Wilken, Jason A.

AU - Baron, Andre T.

AU - Godwin, Andrew K.

AU - Schilder, Russell J.

AU - Singh, Meenakshi

AU - Maihle, Nita Jane

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N2 - Background A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. Methods Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500 mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. Results Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥ 6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. Conclusions This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.

AB - Background A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. Methods Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500 mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. Results Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥ 6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. Conclusions This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.

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