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

Valentina Tuninetti; Luca Pace; Eleonora Ghisoni; Virginia Quarà; Francesca Arezzo; Andrea Palicelli; Vincenzo Dario Mandato; Elena Geuna; Gennaro Cormio; Nicoletta Biglia; Lucia Borsotti; Silvia Gallo; Annamaria Ferrero; Elena Jacomuzzi; Luca Fuso; Jeremy Oscar Smith Pezua Sanjinez; Andrea Puppo; Andrea Caglio; Chiara Rognone; Margherita Turinetto; Giulia Scotto; Massimo Di Maio; Giorgio Valabrega

doi:10.20944/preprints202306.0937.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 12 June 2023 / Approved: 13 June 2023 / Online: 13 June 2023 (12:27:39 CEST)

Background: There is poor evidence about sensitivity to chemotherapy according to microsatellite instability (MSI)/mismatch repair (MMR) status in endometrial cancer (EC). 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: 312 patients treated between 2010-2022 in 4 high volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (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%). 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 difference in PFS (p=0.21) and OS (p=0.057) were detected, although 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 a significantly worse OS.

Endometrial cancer; microsatellite instability; mismatch repair deficiency; platinum-based chemotherapy

Medicine and Pharmacology, Oncology and Oncogenics

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

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