Disease course of dMMR endometrial cancer in real-world clinical practice.

Abstract

e17646 Background: Mismatch repair deficient (dMMR) endometrial cancer represents a distinct molecular subgroup with a different disease course. With the addition of immunotherapy to the first-line chemotherapy, the treatment paradigm for advanced or recurrent dMMR endometrial cancer changed drastically, improving survival. This abstract aims to chart the series of treatments these patients received in our center to better understand the optimal sequencing and strategies combination. Methods: 31 patients with confirmed dMMR endometrial cancer treated in our center with a date of diagnosis after 1/1/2017 were included. Data on demographics, clinical characteristics, treatment details, and adverse events were collected. Statistical analysis was done using SPSS software. Results: Thirty-one patients were identified with a median age at diagnosis of 64.7 years, with 71% of them diagnosed with stage III-IV disease. Patients and tumor characteristics are summarized in Table 1. 28 of them were treated with immunotherapy (IO) in the metastatic setting, 20 (71.4%) as 1 st line in combination with chemotherapy, and 8 (28.6%) as 2 nd line monotherapy. The mPFS of patients receiving IO in 1 st line was not reached, while in 2 nd line mPFS was 4.2 months (95% CIs 0.2-8.1 months) with a p-value of 0.007. When stratified by type of Immunohistochemically defined MMR deficiency, no significant difference in mPFS was noted. More specifically, MLH1/PMS2 loss patients had mPFS of 12.5 months (95% CI 4.8-20.2 months), PMS2 loss only patients had mPFS of 6.8 months while for MSH6/MSH2 loss patients mPFS was not reached (p=0.442). We also stratified patients by ER expression and TP53 mutation status. mPFS was not reached in ER (+) patients and was 12.5 months (95% CIs 0-27.6 months) in ER (-) (p=0.501). Moreover, p53mut patients had an mPFS in IO treatment of 1.7 months (95% CIs 1.9-2.6 months), whereas mPFS of the p53wt population was not reached (p=0.16). Finally, the mOS in patients that received IO in 1 st line was 48.7 months (95% CIs 46.4-51 months) and 27.2 months (95% CIs 4.5-50 months) in those receiving IO in 2 nd line (p=0.699). Conclusions: Real world evidence in the Greek population confirms the efficacy of Immunotherapy in the dMMR population of endometrial cancer patients. We did not identify in our cohort predictive factors related to the type of dMMR according to immunohistochemistry, ER expression and presence of TP53 mutations, despite the sample size precluding definitive conclusions. However, there is a trend favoring treatment with IO in 1st line and decreased efficacy in TP53 mutations that warrants further investigation. Patients’ characteristics No. of patients- related N % Stage at diagnosis  I-II 9 (29%)  III 12 (38.7%)  IV 10 (32.3%) Grade  I-II 19 (61.3%)  III 12 (38.7%) dMMR IHC status  MLH1/PMS2 loss 24 (77.4%)  PMS2 loss 2 (6.2%)  MSH2/MSH6 loss 4 (12.9%)  Unknown 1 (3.2%) ER status  (+) 16 (51.6%)  (-) 15 (48.4%) TP53 mutation  Present 3 (9.7%)  Absent 28 (90.3%)