The effect of progestin therapy in advanced and recurrent endometrial cancer: a systematic review and meta-analysis

Willem Jan Van Weelden; Philine B Birkendahl; Roy I Lalisang; Joanna Inthout; Roy F P M Kruitwagen; Andrea Romano; Johanna M A Pijnenborg

doi:10.1111/1471-0528.17331

The effect of progestin therapy in advanced and recurrent endometrial cancer: a systematic review and meta-analysis

Willem Jan Van Weelden^*, Philine B Birkendahl, Roy I Lalisang, Joanna Inthout, Roy F P M Kruitwagen, Andrea Romano, Johanna M A Pijnenborg

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

Abstract

BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades. Yet, there is limited evidence on response prediction with biomarkers and toxicity.

OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumor grade.

SEARCH STRATEGY: We used the search terms "Endometrial cancer", "Progestins", "Disease progression", "Recurrence" and related terms in Pubmed, Embase and Cochrane databases.

SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, <10 cases and sarcoma histology were excluded.

DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomized studies and the ROBINS-I tool for non-randomized studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate (CBR) and toxicity as primary outcome measures.

MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95%-CI: 25-36), the clinical benefit rate was 52% (95%-CI: 42-61). In PR-positive EC, the ORR was 55%, compared to 12% in PR-negative disease (risk difference 43%, 95%-CI: 15-71). Severe toxicity occurred in 6.5%.

CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR positive disease. The role of PR expression in relation to progression free survival and overall survival is unclear.

Original language	English
Pages (from-to)	143-152
Number of pages	10
Journal	Bjog-an International Journal of Obstetrics and Gynaecology
Volume	130
Issue number	2
Early online date	20 Oct 2022
DOIs	https://doi.org/10.1111/1471-0528.17331
Publication status	Published - Jan 2023

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Van Weelden, W. J., Birkendahl, P. B., Lalisang, R. I., Inthout, J., Kruitwagen, R. F. P. M., Romano, A., & Pijnenborg, J. M. A. (2023). The effect of progestin therapy in advanced and recurrent endometrial cancer: a systematic review and meta-analysis. Bjog-an International Journal of Obstetrics and Gynaecology, 130(2), 143-152. https://doi.org/10.1111/1471-0528.17331

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abstract = "BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades. Yet, there is limited evidence on response prediction with biomarkers and toxicity.OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumor grade.SEARCH STRATEGY: We used the search terms {"}Endometrial cancer{"}, {"}Progestins{"}, {"}Disease progression{"}, {"}Recurrence{"} and related terms in Pubmed, Embase and Cochrane databases.SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, <10 cases and sarcoma histology were excluded.DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomized studies and the ROBINS-I tool for non-randomized studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate (CBR) and toxicity as primary outcome measures.MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95%-CI: 25-36), the clinical benefit rate was 52% (95%-CI: 42-61). In PR-positive EC, the ORR was 55%, compared to 12% in PR-negative disease (risk difference 43%, 95%-CI: 15-71). Severe toxicity occurred in 6.5%.CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR positive disease. The role of PR expression in relation to progression free survival and overall survival is unclear.",

author = "{Van Weelden}, {Willem Jan} and Birkendahl, {Philine B} and Lalisang, {Roy I} and Joanna Inthout and Kruitwagen, {Roy F P M} and Andrea Romano and Pijnenborg, {Johanna M A}",

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doi = "10.1111/1471-0528.17331",

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The effect of progestin therapy in advanced and recurrent endometrial cancer: a systematic review and meta-analysis. / Van Weelden, Willem Jan; Birkendahl, Philine B; Lalisang, Roy I et al.
In: Bjog-an International Journal of Obstetrics and Gynaecology, Vol. 130, No. 2, 01.2023, p. 143-152.

Research output: Contribution to journal › (Systematic) Review article › peer-review

TY - JOUR

T1 - The effect of progestin therapy in advanced and recurrent endometrial cancer

T2 - a systematic review and meta-analysis

AU - Van Weelden, Willem Jan

AU - Birkendahl, Philine B

AU - Lalisang, Roy I

AU - Inthout, Joanna

AU - Kruitwagen, Roy F P M

AU - Romano, Andrea

AU - Pijnenborg, Johanna M A

PY - 2023/1

Y1 - 2023/1

N2 - BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades. Yet, there is limited evidence on response prediction with biomarkers and toxicity.OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumor grade.SEARCH STRATEGY: We used the search terms "Endometrial cancer", "Progestins", "Disease progression", "Recurrence" and related terms in Pubmed, Embase and Cochrane databases.SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, <10 cases and sarcoma histology were excluded.DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomized studies and the ROBINS-I tool for non-randomized studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate (CBR) and toxicity as primary outcome measures.MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95%-CI: 25-36), the clinical benefit rate was 52% (95%-CI: 42-61). In PR-positive EC, the ORR was 55%, compared to 12% in PR-negative disease (risk difference 43%, 95%-CI: 15-71). Severe toxicity occurred in 6.5%.CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR positive disease. The role of PR expression in relation to progression free survival and overall survival is unclear.

AB - BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades. Yet, there is limited evidence on response prediction with biomarkers and toxicity.OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumor grade.SEARCH STRATEGY: We used the search terms "Endometrial cancer", "Progestins", "Disease progression", "Recurrence" and related terms in Pubmed, Embase and Cochrane databases.SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, <10 cases and sarcoma histology were excluded.DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomized studies and the ROBINS-I tool for non-randomized studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate (CBR) and toxicity as primary outcome measures.MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95%-CI: 25-36), the clinical benefit rate was 52% (95%-CI: 42-61). In PR-positive EC, the ORR was 55%, compared to 12% in PR-negative disease (risk difference 43%, 95%-CI: 15-71). Severe toxicity occurred in 6.5%.CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR positive disease. The role of PR expression in relation to progression free survival and overall survival is unclear.

U2 - 10.1111/1471-0528.17331

DO - 10.1111/1471-0528.17331

M3 - (Systematic) Review article

C2 - 36264251

SN - 1470-0328

VL - 130

SP - 143

EP - 152

JO - Bjog-an International Journal of Obstetrics and Gynaecology

JF - Bjog-an International Journal of Obstetrics and Gynaecology

IS - 2

ER -

The effect of progestin therapy in advanced and recurrent endometrial cancer: a systematic review and meta-analysis

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