Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials

Zachary A Kopelman; Chunqiao Tian; Jordyn Tumas; Neil T Phippen; Christopher M Tarney; Erica R Hope; Stuart S Winkler; Suzanne Jokajtys; Calen W Kucera; John K Chan; Michael T Richardson; Daniel S Kapp; Chad A Hamilton; Charles A Leath 3rd; Nathaniel L Jones; Rodney P Rocconi; John H Farley; Angeles Alvarez Secord; Casey M Cosgrove; Matthew A Powell; Ann Klopp; Joan L Walker; Gini F Fleming; Nicholas W Bateman; Thomas P Conrads; G Larry Maxwell; Kathleen M Darcy

doi:10.1016/j.ygyno.2024.03.026

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials

Gynecol Oncol. 2024 Apr 8:183:103-114. doi: 10.1016/j.ygyno.2024.03.026. Online ahead of print.

Authors

Zachary A Kopelman¹, Chunqiao Tian², Jordyn Tumas¹, Neil T Phippen¹, Christopher M Tarney¹, Erica R Hope³, Stuart S Winkler³, Suzanne Jokajtys¹, Calen W Kucera¹, John K Chan⁴, Michael T Richardson⁵, Daniel S Kapp⁶, Chad A Hamilton⁷, Charles A Leath 3rd⁸, Nathaniel L Jones⁹, Rodney P Rocconi¹⁰, John H Farley¹¹, Angeles Alvarez Secord¹², Casey M Cosgrove¹³, Matthew A Powell¹⁴, Ann Klopp¹⁵, Joan L Walker¹⁶, Gini F Fleming¹⁷, Nicholas W Bateman¹⁸, Thomas P Conrads¹⁹, G Larry Maxwell²⁰, Kathleen M Darcy²¹

Affiliations

¹ Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA.
² Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; The Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
³ Division of Gynecologic Oncology, Department of Gynecologic Surgery and Obstetrics, Brooke Army Medical Center, San Antonio, TX, USA.
⁴ Palo Alto Medical Foundation, California Pacific Medical Center, Sutter Health, San Francisco, CA, USA.
⁵ Department of Obstetrics and Gynecology, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
⁶ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Gynecologic Oncology Section, Women's Services and The Ochsner Cancer Institute, Ochsner Health, New Orleans, LA, USA.
⁸ Division of Gynecologic Oncology, University of Alabama at Birmingham, O'Neal Comprehensive Cancer Center, Birmingham, AL, USA.
⁹ Division of Gynecologic Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA.
¹⁰ Division of Gynecologic Oncology, Cancer Center & Research Institute, the University of Mississippi Medical Center, Jackson, MS, USA.
¹¹ Division of Gynecologic Oncology, Center for Women's Health, Cancer Institute, Dignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
¹² Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
¹³ Division of Gynecologic Oncology, The Ohio State University, Columbus, OH, USA.
¹⁴ Division of Gynecologic Oncology, Siteman Cancer Center, Washington University, St Louis, MO, USA.
¹⁵ Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁶ Gynecologic Oncology Division, Stephenson Cancer Center, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA.
¹⁷ Department of Medicine, University of Chicago, Chicago, IL, USA.
¹⁸ Division of Gynecologic Oncology, Center for Women's Health, Cancer Institute, Dignity Health St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA; The Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
¹⁹ Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; The Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, Falls Church, VA, USA.
²⁰ Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; The Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, Falls Church, VA, USA. Electronic address: George.Maxwell@inova.org.
²¹ Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD, USA; The Henry M Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA. Electronic address: darcyk@whirc.org.

PMID: 38593674
DOI: 10.1016/j.ygyno.2024.03.026

Abstract

Objective: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).

Methods: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death.

Results: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status.

Conclusions: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Keywords: AACR GENIE; Endometrioid endometrial cancer; NCDB; Racial disparities; Randomized phase III clinical trial; SEER.