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SO018/#362  Molecular classification of endometrial cancers (EC) and association with relapse-free survival (RFS) outcomes: ancillary analysis of GOG-0258
  1. Aine Clements1,
  2. Danielle Enserro2,
  3. Kyle Strickland3,
  4. Rebecca Previs4,
  5. Paul Disilvestro5,
  6. Nick Spirtos6,
  7. Casey Cosgrove7,
  8. Greg Sfakianos8,
  9. J Liu9,
  10. Roberto Vargas10,
  11. Mark Shahin11,
  12. Bradley Corr12,
  13. Linda Van Le13,
  14. Frederick Ueland14,
  15. David Warshal15,
  16. Jessica Gillen16 and
  17. Angeles Alvarez Secord17
  1. 1OhioHealth, Ob/gyn, Columbus, USA
  2. 2Roswell Park, Clinical Trials Development, Buffalo, USA
  3. 3Duke University, Pathology, Durham, USA
  4. 4Labcorp, Medical Affairs, Chapel Hill, USA
  5. 5Women and Infants, Gynecologic Oncology, Providence, USA
  6. 6Women’s Cancer Center of Nevada, Gynecologic Oncology, Las Vegas, USA
  7. 7The Ohio State University, Gynecologic Oncology, Columbus, USA
  8. 8Piedmont Columbus Midtown JBACC Medical Oncology, Gynecologic Oncology, Columbus, USA
  9. 9Cancer Research Consortium of Michigan, Gynecologic Oncology, Ann Arbor, USA
  10. 10Women’s Health Institute at The Cleveland Clinic, Gynecologic Oncology, Cleveland, USA
  11. 11Hanjani Institute for Gynecologic Oncology Abington Memorial Hospital, Gynecologic Oncology, Abington, USA
  12. 12University of Colorado, Obstetrics and Gynecology, Aurora, USA
  13. 13University of North Carolina at Chapel Hill, Gynecologic Oncology, Chapel Hill, USA
  14. 14University of Kentucky, Gynecologic Oncology, Lexington, USA
  15. 15Cooper Hospial University Medical Center, Gynecologic Oncology, Camden, USA
  16. 16Cancer Research for the Ozarks, Gynecologic Oncology, Springfield, USA
  17. 17Duke University, Gynecologic Oncology, Durham, USA


Introduction Determine whether molecular classification using mismatch repair (MMR) and p53 protein expression predictsRFS in EC patients treated with chemotherapy and radiation (CRT) versus chemotherapy (CT).

Methods GOG-0258 was a phase III, randomized trial (NCT00942357) comparing CRT and CT with primary endpoint of RFS. Immunohistochemistry was performed to determine MMR and p53 status. Demographic variables were compared with chi-squared and Kruskal Wallis tests for categorical and continuous variables, respectively. Kaplan-Meier curves estimated RFS between sub-groups. Adjusted Cox proportional hazards models estimated hazard ratios and 95% confidence limits.

Results Using a modified ProMiSe algorithm, 27.4% of EC classified as dMMR, 49% p53wt, and 23.6% p53abn. p53abn tumors were more frequent in older (p<0.001ADD p-value) and Black (p<0.001ADD p-value) patients, and those with serous histology (p<0.001ADD p-value). In contrast, dMMR was more common in Non-Hispanic patients (ADD p-valuep=0.025) and endometrioid cancers (p<0.001ADD p-value). 5-year RFS was significantly worse for those with p53abn [28.8% vs 68.9% vs 57.5%; HR=3.39 (2.34–4.91); p<0.001] compared to p53wt (referent) and dMMR ECs. After adjusting for age, gross residual disease, and treatment,p53wt was associated with improved RFS in the CRT compared to CT group [77.2% vs 59.7%; HR=0.54 (0.32–0.94); p=0.02]. The 5-year RFS with CRT versus CT were similar for those with p53abn [29.3% vs 29.4%; 0.76 (0.46–1.24)] and dMMR [52.5% vs 63.7% (0.70–2.57)] ECs.

Conclusion/Implications Molecular classification is prognostic in EC, with worse RFS in p53abn tumors. In an exploratory analysis, p53wt appears to be predictive for treatment efficacy favoring CRT over CT. Further trials are warranted to confirm these findings.

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