Introduction/Background There is little evidence about sensitivity to chemotherapy (CT) according to microsatellite instability (MSI) high (h)/mismatch repair (MMR) deficiency (d) status in patients with endometrial cancer (EC).
Methodology The RAME study is a retrospective analysis aiming to assess response to CT in MSI-h/dMMR and MSI-low(l)/proficient (p)MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with no advanced disease at diagnosis and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease.
Results 312 patients treated between January 2010 and January 2022 in 4 high volume MITO centers were selected. 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%), mainly detected with immunohistochemistry (92%). Median age was 65 (31–91) years. At diagnosis, no difference in terms of age (p=0.26), FIGO stage (p=0.43) and comorbidities (p=0.66) were identified between MSI-h/dMMR and MSI-low/pMMR. Among the 278 patients with no metastatic disease at diagnosis, median RFS was 100.0 months (95%CI 59.4–140.7) for MSI-l/pMMR and 120.9 months (60.0–181.8) for MSI-h/dMMR (Hazard Ratio 0.81, 95%CI 0.50–1.31, p=0.39). Seventy-seven patients received first-line CT for advanced/recurrent disease, 76.6% (59/77) received platinum-based CT and 19.5% (15/77) were MSI-l/pMMR. In this setting, median PFS was 10.3 months (95%CI 7.7–12.8) and median OS was 37.2 months (95%CI 28.0–46.4) for MSI-l/pMMR; median PFS was 6.3 months (95%CI 2.0–10.6) and median OS was 14.0 months (95%CI 1.0–27.1) for MSI-h/dMMR, with a significantly worse OS in MSI-h/dMMR patients (HR 2.26, 95% IC 1.04 – 4.92, p=0.039). In the subgroup of patients receiving platinum-based CT, no statistically significant difference in PFS (p=0.21) and OS (p=0.057) were detected but PFS and OS were numerically longer in the MSI-l/pMMR population.
Conclusion Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had numerically worse PFS and OS in comparison with MSH-l/pMMR EC.
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