Abstract B017: Disease free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant chemotherapy
Authors: Kalé Kponee-Shovein, Vimalanand S. Prabhu, Yan Song, Lei Chen, Mu Cheng, Yeran Li, Yezhou Sun, Annalise Hilts, Qi Hua, Jasmine Lichfield, Linda Duska
Journal: Clinical Cancer Research (2024)

Abstract Introduction: Disease-free survival (DFS) is often evaluated as a primary endpoint in early settings for several cancers, including endometrial cancer (EC). However, the role of DFS as a potential predictor of overall survival (OS) in EC is unknown. Elucidating the association between DFS and OS in EC is critical for contextualizing findings from trials where DFS is a primary endpoint, such as KEYNOTE-B21, which assesses the effect of treatment with pembrolizumab + adjuvant chemotherapy (CTX) vs. adjuvant CTX, with or without radiotherapy in patients with EC at high risk of recurrence. This real-world study assessed the association between DFS and OS and the impact of recurrence on OS in elderly patients with EC at high risk of recurrence receiving adjuvant CTX. Methods: SEER-Medicare data (2007–2019) were used to identify patients with EC at high risk of recurrence who received adjuvant CTX with or without radiotherapy. Patients were defined as high risk of recurrence if they had either Stage I or II EC with non-endometroid histology or Stage III or IVA EC with any histology. An EC recurrence was defined as having a diagnosis with a distinct secondary cancer &amp;gt;90 days after end of adjuvant CTX or receipt of additional cancer treatment &amp;gt;90 days after end of adjuvant CTX. Kaplan-Meier (KM) analyses were used to estimate OS (time from initiation of adjuvant therapy [index date] to death) and DFS (time from index date to earliest of recurrence or death). The correlation between DFS and OS was assessed using Kendall’s τ rank correlation. Landmark analyses were used to compare OS between patients with vs. without a recurrence at 1-, 3-, and 5-years post the index date; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using adjusted Cox models. KM analyses were used to estimate OS from a recurrence (index date) for recurrent patients and from an imputed index date (using frequency matching) for non-recurrent patients. Results: Of 794 eligible patients, 253 (31.9%) experienced a recurrence over a median follow up of 3.6 years. Median age at diagnosis was 71.9 years, 69.8% had stage I/II disease, and 86.6% had non-endometrioid carcinoma. Median OS was not reached (5-year OS: 72.5%) and median DFS was 7.9 years (5-year DFS: 58.7%). A significant positive correlation between DFS and OS was observed (Kendall’s τ =0.83; 95% CI: 0.79–0.86; p&amp;lt;0.001). Patients with a recurrence had significantly higher risk of death than those without, at landmark points 1- (HR: 4.4; 95% CI: 2.8–7.0; p&amp;lt;.001), 3- (HR: 5.2; 95% CI: 3.1–8.7; p&amp;lt;.001), and 5-years (HR: 5.1; 95% CI: 2.2–11.7; p&amp;lt;.001). Patients with a recurrence had significantly shorter median OS than those without (median OS: 1.4 years vs. not reached; p&amp;lt;.001). Conclusions: In elderly patients with EC at high risk of recurrence who received adjuvant CTX, DFS was strongly correlated with OS and having a recurrence was associated with significantly higher risk of death. Our findings suggest that DFS is a strong predictor of OS in this population and may be a useful surrogate endpoint. Citation Format: Kalé Kponee-Shovein, Vimalanand S. Prabhu, Yan Song, Lei Chen, Mu Cheng, Yeran Li, Yezhou Sun, Annalise Hilts, Qi Hua, Jasmine Lichfield, Linda Duska. Disease free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant chemotherapy [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B017.