Journal article
A Surgical Window Trial Evaluating Medroxyprogesterone Acetate with or without Entinostat in Patients with Endometrial Cancer and Validation of Biomarkers of Cellular Response
Clinical cancer research, Vol.27(10), pp.2734-2741
05/15/2021
DOI: 10.1158/1078-0432.CCR-20-4618
PMCID: PMC8127359
PMID: 33766814
Abstract
This surgical window of opportunity (window) study assessed the short-term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma.
This multisite, randomized, open-label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21-24. Pretreatment and posttreatment tissue was assessed for PR H-scores, Ki-67 levels, and histologic response.
Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H-scores were significantly lower than pretreatment H-scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively,
= 0.87). Decreased Ki-67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone (
= 0.13). Median PR H-score decreases were larger when Ki-67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki-67 nuclear staining, consistent with reduced cellular proliferation (
< 0.008).
This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki-67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short-term study, lessons learned can inform future window and treatment trials.
Details
- Title: Subtitle
- A Surgical Window Trial Evaluating Medroxyprogesterone Acetate with or without Entinostat in Patients with Endometrial Cancer and Validation of Biomarkers of Cellular Response
- Creators
- Linda R Duska - University of VirginiaVirginia L Filiaci - Roswell Park Cancer InstituteJoan L Walker - University of OklahomaLaura L Holman - University of OklahomaEmily K Hill - University of Iowa Hospitals and ClinicsRichard G Moore - University of RochesterKari L Ring - University of VirginiaMichael L Pearl - Stony Brook UniversityCarolyn Y Muller - University of New Mexico HospitalChristina L Kushnir - Department of Obstetrics and Gynecology, Women's Cancer Center, Las Vegas, Nevada.Heather A Lankes - The Ohio State University Wexner Medical CenterMegan I Samuelson - University of Iowa Hospitals and ClinicsKelley S Carrick - Southwestern Medical CenterAnand Rajan - University of Iowa Hospitals and ClinicsWilliam H Rodgers - Cornell UniversityElise C Kohn - Cancer Therapy Evaluation Program, NCI, Rockville, Maryland.Richard Piekarz - Cancer Therapy Evaluation Program, NCI, Rockville, Maryland.Kimberly K Leslie - University of Iowa Hospitals and Clinics
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.27(10), pp.2734-2741
- DOI
- 10.1158/1078-0432.CCR-20-4618
- PMID
- 33766814
- PMCID
- PMC8127359
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- U10 CA180822 / NCI NIH HHS U10 CA180868 / NCI NIH HHS U24 CA196067 / NCI NIH HHS UG1 CA189867 / NCI NIH HHS
- Language
- English
- Date published
- 05/15/2021
- Academic Unit
- Pathology; Obstetrics and Gynecology
- Record Identifier
- 9984186777202771
Metrics
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