Retrospective Analysis of the Correlation of MSI-h/dMMR Status and Response to Therapy for Endometrial Cancer: RAME Study, a Multicenter Experience

SIMPLE SUMMARY: EC is the most common gynecological malignancy, and increased incidence and disease-related mortality have been observed in recent years. Data on the response to first-line carboplatin plus paclitaxel in EC is limited. The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-h/dMMR and MSI-l/pMMR EC patients. In patients receiving platinum-based chemotherapy in a first-line setting, PFS and OS were numerically longer in the MSI-l/pMMR population compared to MSI-h/dMMR patients. ABSTRACT: Background: There is poor evidence regarding sensitivity to chemotherapy in endometrial cancer (EC) based on microsatellite instability (MSI)/mismatch repair (MMR) status. Methodology: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h)/deficient (d) MMR and MSI-low (l)/proficient (p) MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. Results: A total of 312 patients treated between 2010 and 2022 in four high-volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. In total, 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31–91) years. Among patients with localized disease, 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 (p = 0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p = 0.039). In patients receiving platinum-based chemotherapy, no statistically significant differences in PFS (p = 0.21) or OS (p = 0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. Conclusions: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.