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. 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.

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

Tuninetti, Valentina;Pace, Luca;Ghisoni, Eleonora;Quarà, Virginia;Palicelli, Andrea;Geuna, Elena;Biglia, Nicoletta;Borsotti, Lucia;Gallo, Silvia;Ferrero, Annamaria;Jacomuzzi, Elena;Fuso, Luca;Pezua Sanjinez, Jeremy Oscar Smith;Caglio, Andrea;Rognone, Chiara;Turinetto, Margherita;Scotto, Giulia;Di Maio, Massimo;Valabrega, Giorgio
2023-01-01

Abstract

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. 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.
2023
Jul 15
14
1
11
endometrial cancer; microsatellite instability; mismatch repair deficiency; platinum-based chemotherapy
Tuninetti, Valentina; Pace, Luca; Ghisoni, Eleonora; Quarà, Virginia; Arezzo, Francesca; Palicelli, Andrea; Mandato, Vincenzo Dario; Geuna, Elena; Cormio, Gennaro; Biglia, Nicoletta; Borsotti, Lucia; Gallo, Silvia; Ferrero, Annamaria; Jacomuzzi, Elena; Fuso, Luca; Pezua Sanjinez, Jeremy Oscar Smith; Puppo, Andrea; Caglio, Andrea; Rognone, Chiara; Turinetto, Margherita; Scotto, Giulia; Di Maio, Massimo; Valabrega, Giorgio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1926796
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