Real-world outcomes by DNA mismatch repair (MMR) status in patients (pts) with high-risk endometrial cancer (EC) in the adjuvant setting.

Abstract

e17623 Background: EC is the sixth most common cancer in women. Pts with high-risk EC are more susceptible to recurrence. Per ESMO guidelines, high-risk subtypes without macroscopic residual disease following surgical resection are defined as: International Federation of Gynecology and Obstetrics (FIGO) Stages I–IVA with p53 abnormalities or serous/undifferentiated carcinoma with myometrial invasion and Stages III–IVA. Defects in MMR occur in ~30% of pts with EC; however, there is conflicting evidence on the effect of MMR status on clinical outcomes and its utility to guide adjuvant therapy decisions. We report real-world disease-free survival (rwDFS) and overall survival (rwOS) by MMR status in pts with high-risk EC. Methods: This retrospective observational study included pts with treatment-naïve, high-risk EC without residual disease following surgical resection from the nationwide Flatiron Health electronic health record-derived, de-identified database. Pts were diagnosed Jan 2018–Dec 2023, underwent a hysterectomy (index date), and initiated adjuvant chemotherapy within 4 months. As data on p53 abnormalities were limited, human epidermal growth factor receptor 2 expression (positive/equivocal) was used as a proxy. The primary and secondary endpoints were rwDFS at 36 months and rwOS by MMR status, respectively. Results: Overall, 599 pts were identified; 70.5% were aged >60 years and 96.5% had Stage III disease at diagnosis. Most pts had endometrioid (62.8%) or serous (20.0%) carcinoma; 29.7% had MMR-deficient (dMMR) and 70.3% had MMR-proficient (pMMR) EC. 416 (69.4%) pts received radiotherapy (prior to or post index date). At 36 months from the index date, rwDFS (95% CI) was 58.2% (53.6, 63.1) in all pts and 71.6% (64.5, 79.4) and 51.7% (46.1, 58.0) in those with dMMR and pMMR EC, respectively. Landmark rwDFS and rwOS at 12, 24, and 36 months are shown in the Table. Conclusions: Poor rwDFS and rwOS was observed in pts with high-risk EC, particularly in those with pMMR vs dMMR EC. Although low numbers of pts with early-stage disease limit broader population insights, these findings highlight the potential need to further evaluate existing treatments and explore novel therapeutic strategies in the adjuvant setting. All dMMR pMMR n 599 178 421 Median rwDFS, months (IQR) 48.2 (44.4, not estimable [NE]) 66.0 (55.8, NE) 39.5 (30.2, 54.4) rwDFS at 12 months, % (95% CI) 82.9 (79.8, 86.1) 86.7 (81.6, 92.0) 81.3 (77.5, 85.3) rwDFS at 24 months, % (95% CI) 66.0 (61.9, 70.4) 74.4 (67.7, 81.7) 62.3 (57.2, 67.8) rwDFS at 36 months, % (95% CI) 58.2 (53.6, 63.1) 71.6 (64.5, 79.4) 51.7 (46.1, 58.0) Median rwOS, months (IQR) Not reached (NR) NR 62.7 (54.2, NE) rwOS at 12 months, % (95% CI) 95.8 (94.1, 97.5) 97.6 (95.3, 100.0) 95.0 (92.8, 97.2) rwOS at 24 months, % (95% CI) 86.2 (83.1, 89.4) 94.0 (90.3, 97.9) 82.7 (78.6, 87.0) rwOS at 36 months, % (95% CI) 76.7 (72.5, 81.1) 90.4 (85.4, 95.6) 70.0 (64.5, 76.0)