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Clinical Trial
. 2010 Jan;116(1):15-20.
doi: 10.1016/j.ygyno.2009.09.025. Epub 2009 Oct 18.

Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study

Gini F Fleming  1 , Michael W Sill, Kathleen M Darcy, D Scott McMeekin, J Tate Thigpen, Lisa M Adler, Jonathan S Berek, Julia A Chapman, Paul A DiSilvestro, Ira R Horowitz, James V Fiorica
Affiliations
Clinical Trial

Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study

Gini F Fleming et al. Gynecol Oncol. 2010 Jan.

Abstract

Purpose: This study evaluated efficacy of single-agent trastuzumab against advanced or recurrent HER2-positive endometrial carcinoma (EC), and explored predictors for HER2 amplification.

Patients and methods: Eligible patients had measurable stage III, IV, or recurrent EC. There was no limit on prior therapy although total prior doxorubicin dose was limited to 320 mg/m(2). Tumors were required to have HER2 overexpression (2+ or 3+ immunohistochemical staining) or HER2 amplification (FISH HER2/CEP 17 ratio >2.0). Trastuzumab was administered intravenously at a dose of 4 mg/kg in week 1, then 2 mg/kg weekly until disease progression. The primary endpoint was tumor response.

Results: Of the 286 tumors centrally screened by LabCorp, 33 (11.5%) were HER2-amplified. Three of 8 clear (38%) cell carcinomas and 7 of 25 serous carcinomas (28%) screened exhibited HER2 amplification compared with 7% (2/29) of endometrioid adenocarcinomas. HER2 overexpression was correlated with HER2 amplification (r=0.459; p<0.0001). Thirty-four women were enrolled; 1 was excluded (refused treatment); and 18 had tumors with known HER2 amplification. No major tumor responses were observed. Twelve women experienced stable disease, 18 had increasing disease, and 3 were indeterminate for tumor response. Neither HER2 overexpression nor HER2 amplification appeared to be associated with progression-free survival or overall survival.

Conclusion: Trastuzumab as a single agent did not demonstrate activity against endometrial carcinomas with HER2 overexpression or HER2 amplification, although full planned accrual of women with HER2 amplified tumors was not achieved due to slow recruitment. Serous and clear cell endometrial carcinomas appear to be more likely to demonstrate HER2 amplification.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
a. Summary of HER2 testing results on patients screened (left side of figure) and patients enrolled (right side of figure) b. Cases Screened by LabCorp during Period A with Evaluable IHC and FISH Data
Figure 1
Figure 1
a. Summary of HER2 testing results on patients screened (left side of figure) and patients enrolled (right side of figure) b. Cases Screened by LabCorp during Period A with Evaluable IHC and FISH Data
Figure 2
Figure 2
Progression-free survival (panels A and C) and overall survival (panels B and D) and for patients treated on study and categorized by HER2 overexpression as 2+ or 3+ IHC (panels A and B) or HER2 amplification as low or high FISH (panels C and D).
Figure 2
Figure 2
Progression-free survival (panels A and C) and overall survival (panels B and D) and for patients treated on study and categorized by HER2 overexpression as 2+ or 3+ IHC (panels A and B) or HER2 amplification as low or high FISH (panels C and D).
Figure 2
Figure 2
Progression-free survival (panels A and C) and overall survival (panels B and D) and for patients treated on study and categorized by HER2 overexpression as 2+ or 3+ IHC (panels A and B) or HER2 amplification as low or high FISH (panels C and D).
Figure 2
Figure 2
Progression-free survival (panels A and C) and overall survival (panels B and D) and for patients treated on study and categorized by HER2 overexpression as 2+ or 3+ IHC (panels A and B) or HER2 amplification as low or high FISH (panels C and D).
See this image and copyright information in PMC

Comment in

References

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