Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Feb:193:119-129.
doi: 10.1016/j.ygyno.2025.01.006. Epub 2025 Jan 23.

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258

Aine Clements  1 , Danielle Enserro  2 , Kyle C Strickland  3 , Rebecca Previs  4 , Daniela Matei  5 , David Mutch  6 , Matthew Powell  7 , Ann Klopp  8 , David Scott Miller  9 , William Small Jr  10 , Paul DiSilvestro  11 , Nick Spirtos  12 , Casey Cosgrove  13 , Greg Sfakianos  14 , J Rebecca Liu  15 , Roberto Vargas  16 , Mark Shahin  17 , Bradley Corr  18 , Kimberly Dessources  19 , Frederick Ueland  20 , David Warshal  21 , Jessica Gillen  22 , Angeles Alvarez Secord  23
Affiliations
Clinical Trial

Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) and overall survival (OS) outcomes: Ancillary analysis of GOG-0258

Aine Clements et al. Gynecol Oncol. 2025 Feb.

Abstract

Purpose: Determine if molecular classification using mismatch repair (MMR) and p53 protein expression predicts recurrence-free survival (RFS) and overall survival (OS) in endometrial cancer (EC) patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods: GOG-0258, a phase III randomized trial (NCT00942357), compared CRT to CT. Immunohistochemistry assessed MMR and p53 status. Kaplan-Meier curves and adjusted Cox models analyzed survival outcomes by molecular subtype.

Results: ECs classified as deficient MMR (dMMR) (27 %), p53 abnormal (p53abn) (24 %), and p53 wild type (p53wt) (49 %). p53abn were more frequent in patients that were older, Black, and had serous histology (p < 0.001). Median follow up was 113 months. Five-year RFS and OS were worse with p53abn (29 % [Hazard Ratio (HR) = 3.39 (95 % Confidence Interval (CI): 2.34-4.91)] and 39 % [HR = 4.64 (95 % CI: 3.16-6.79)] compared to those with p53wt (referent) (p < 0.001). The five-year RFS and OS for dMMR cancers were (58 % [HR = 1.30 (95 % CI: 0.85-1.97)] and 77 % [HR = 1.53 (95 % CI: 0.99-2.36)] compared to those with p53wt (69 % and 85 %). After adjusting for age, gross residual disease, and treatment, p53wt improved RFS with CRT compared to CT in an exploratory analysis (77 % vs 60 %; HR = 0.54 (95 % CI: 0.32-0.94). The 5-year and 10-year OS rates were similar in CRT compared to CT in all subgroups.

Conclusion: Molecular classification appears to be predictive and prognostic, with worse survival in those with p53abn tumors. In an exploratory analysis, p53wt appears to predict improved RFS, favoring CRT over CT. There was no difference in treatment efficacy based on molecular subtype for OS.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest Dr. Aine Clements received payment to Duke for tumor testing for research project from American Association of OB/Gyn Foundation Bridge Award, Ohio Health Research Institute Agreement, and Kay Yow Cancer Fund/The V Foundation for Cancer Research. Dr. Danielle Enserro received Cooperative group/NCTN Grant Funding for all aspects of this trial, including travel to Group meetings, study monitoring, statistical analysis, manuscript writing, etc. Dr. Kyle C. Strickland received support to attend meetings from Labcorp. He also owns Labcorp stock and is employed by Labcorp. Dr. Rebecca A. Previs received support to attend meetings from Labcorp. She also owns Labcorp stock and is employed by Labcorp. Dr. David Mutch received an NIH p50 Route 66 Endometrial SPORE P50CA265793 grant/contract. Dr. Matthew Powell received consulting fees from GSK, Merck, AstraZeneca, Aadi Bioscience, Genmab, Seagen and Eisai. Dr. David S. Miller's institution received grants/contracts from Advenchen, Forty Seen, Merck, Syros, US BIOTEST, Regeneron and Karyopharm. He also received consulting fees from Karyopharm, Incyte, Eisai, Merck, GlaxoSmithKline and Immunogen. Dr. Casey Cosgrove's institution received research support from GSK. She received payment for authorship from UpToDate. She received personal consulting fees from GSK, Intuitive and Merck. She received support for attending meetings and/or travel from the GOG. She also participated on an Advisory Board from GSK. Dr. Mark S. Shahin received consulting fees from GSK, AZ, Eisai, Abbvie/Immunogen, Pizer/Genmab. He also has a leadership or fiduciary role in Unite For Her. Dr. Bradley Corr participated on Advisory Boards for GSK, Immunogen, AstraZeneca, Eisai, Gilead, Zentalis, Merck and Corecept. Dr. Angeles Alvarez Secord's institution received clinical trial grants from Abbvid, Aravive, AstraZeneca, Clovis, Eisai, Ellipses GSK, I-MAB Biopharma, Merck, Oncoquest/Canaria Bio, Roche, Genentech, Seagen Inc., VBL Therapeutics and Zentalis. Her institution received grants from Mersana and Myriad for translational research, as well as clinical trial grants and grant for translational research from Immunogen. She received payment to herself for Educational Program events including Curio Science, @Point of Care, Clinical Care Options, ASCO, Peerview, Research to Practice, Bio ASCEND, GOG Foundation, and Clinical HMP Global Great Debates. She personally received support for attending meetings and/or travel to from GOG Foundation, NRG Oncology, Society of Gynecologic Oncology. She has also participated (uncompensated) on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Clovis, Gilead, GSK, Immunogen, Imvax, Merck, Mersana, Natera, Oncoquest/CanariaBio, and Onconova and (compensated) an Advisory Board for AbbVie. She received stock options from Amgen ($570.20) and Johnson & Johnson ($178.96) and royalities from UpToDate. She received payment to herself from GOG Foundation. She received payment from the GOG Foundation Board of Directors; to her institution for serving as NRG Committee Vice Chair; and uncompensated for SGO Board of Directors; FWC Board of Director; AAOGF Board of Trustees and AGOS Council. All other co-authors have no Conflicts of Interest to disclose.

References

    1. https://www.cancer.org/cancer/endometrial-cancer/detection-diagnosis-sta....
    1. Matei D, Filiaci V, Randall ME, et al., Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer, N. Engl. J. Med 380 (2019) 2317–2326. - PMC - PubMed
    1. Daniela E, Matei M, Enserro Daniella, Kudrimoti Mahesh, Steinhoff Margaret, DiSilvestro Paul A., Walker Joan, Kim Byoung-Gie, Powell Matthew A., O’Malley David, Spirtos Nick M., Tewari Krishnansu S., Richards William, Waggoner Steven, Mutch David G., Miller David S., Overall survival in NRG258, a randomized phase III trial of chemoradiation vs. chemotherapy alone for locally advanced endometrial carcinoma (Abstract SGO Annual Meeting), 2023.
    1. de Boer SM, Powell ME, Mileshkin L, et al., Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial, Lancet Oncol 19 (2018) 295–309. - PMC - PubMed
    1. Leon-Castillo A, de Boer SM, Powell ME, et al., Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy, J. Clin. Oncol 38 (2020) 3388–3398. - PMC - PubMed

Publication types

Substances

LinkOut - more resources