A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer

Leslie, Kimberly K.

English

Iowa Research Online

Proceedings in Obstetrics and Gynecology, 2013; 3(3 Supplement):5 
 
*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. A phase II evaluation of gefitinib in the treatment of persistent or recurrent 
endometrial cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2013 Jun;129(3):486-94. doi: 
10.1016/j.ygyno.2013.02.019. Epub 2013 Feb 21. PubMed PMID: 23438670 
This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License 
(http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any 
medium, provided the original work is properly cited. 
1 
 
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 Hanjan, Jason A. Wilken, Andre T. Baron, 
Andrew K. Godwin, Russell J. Schilder, Meenakshi Singh, Nita J. Maihle 
Keywords: Gefitinib; endometrial cancer; epidermal growth factor receptor (EGFR); soluble EGFR; 
estrogen receptor; progesterone receptor 
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 
ERwith PRA in primary and recurrent 
tumors, and pEGFRwith 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. 
This study was supported by the National Cancer 
Institute grants to the Gynecologic Oncology Group 
Proceedings in Obstetrics and Gynecology, 2013; 3(3 Supplement):5 
 
Abstract: A phase II evaluation of gefitinib  2 
 
(GOG) Administrative Office, the GOG Core 
Laboratory for Receptors and Targets and the GOG 
Tissue Bank (CA 27469), the GOG Statistical and 
Data Center (CA 37517), K. Leslie (R01-CA099908), 
A.K. Godwin (R01-CA140323), N. Maihle (R01-
CA79808), as well as support from Susan G Komen 
for the Cure and the Marsha Rivkin Foundation for 
Ovarian Cancer Research (to J. Wilken). We also 
thank and acknowledge the Barbara Beach Fund to 
support endometrial cancer research (to K. Leslie). 


A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study*

Proceedings in Obstetrics and Gynecology

Proceedings in Obstetrics and Gynecology, 2013; 3(3 Supplement):5  *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. A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2013 Jun;129(3):486-94. doi: 10.1016/j.ygyno.2013.02.019. Epub 2013 Feb 21. PubMed PMID: 23438670 This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1  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 Hanjan, Jason A. Wilken, Andre T. Baron, Andrew K. Godwin, Russell J. Schilder, Meenakshi Singh, Nita J. Maihle Keywords: Gefitinib; endometrial cancer; epidermal growth factor receptor (EGFR); soluble EGFR; estrogen receptor; progesterone receptor 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 ERwith PRA in primary and recurrent tumors, and pEGFRwith 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. This study was supported by the National Cancer Institute grants to the Gynecologic Oncology Group Proceedings in Obstetrics and Gynecology, 2013; 3(3 Supplement):5  Abstract: A phase II evaluation of gefitinib  2  (GOG) Administrative Office, the GOG Core Laboratory for Receptors and Targets and the GOG Tissue Bank (CA 27469), the GOG Statistical and Data Center (CA 37517), K. Leslie (R01-CA099908), A.K. Godwin (R01-CA140323), N. Maihle (R01-CA79808), as well as support from Susan G Komen for the Cure and the Marsha Rivkin Foundation for Ovarian Cancer Research (to J. Wilken). We also thank and acknowledge the Barbara Beach Fund to support endometrial cancer research (to K. Leslie). 

https://ir.uiowa.edu/cgi/viewcontent.cgi?article=1226&amp;context=pog

A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: A Gynecologic Oncology Group study*

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