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#305 (R)etrospective (A)nalysis of the correlation of (M)SI-H/DMMR status and response to therapy for (E)ndometrial cancer: RAME study, a multicenter experience
  1. Valentina Tuninetti1,
  2. Luca Pace2,
  3. Eleonora Ghisoni3,
  4. Francesca Arezzo4,
  5. Andrea Palicelli5,
  6. Vincenzo Dario Mandato6,
  7. Gennaro Cormio7,
  8. Elena Geuna8,
  9. Nicoletta Biglia2,
  10. Lucia Borsotti9,
  11. Silvia Gallo9,
  12. Annamaria Ferrero2,
  13. Elena Jacomuzzi2,
  14. Luca Fuso2,
  15. Jeremy Oscar Smith Pezua Sanjinez2,
  16. Andrea Puppo10,
  17. Giulia Scotto11,
  18. Margherita Turinetto11,
  19. Massimo Di Maio1 and
  20. Giorgio Valabrega1
  1. 1Department of Oncology, University of Turin, Medical Oncology, Ordine Mauriziano Hospital, Torino, Italy
  2. 2Obstetrics and Gynaecology Unit, Umberto I Hospital, Department of Surgical Sciences, School of Medicine, University of Turin, Turin, Italy, Torino, Italy
  3. 3Department of Oncology, Immuno-Oncology Service, University Hospital of Lausanne- CHUV, Lausanne, Switzerland, Losanna, Switzerland
  4. 4Department of Precision and Regenerative Medicine – DiMePRe-J, University of Bari ‘Aldo Moro’, Bari, Italy
  5. 5Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy, Reggio Emilia, Italy
  6. 6Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy Italy, Reggio Emilia, Italy
  7. 7Gynecologic Oncology Unit, IRCCS Istituto Tumori ‘Giovanni Paolo II’, Bari, Italy – Interdisciplinar Department of Medicine, University of Bari ‘Aldo Moro’, Bari, Italy
  8. 8Department of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy., Candiolo, Italy
  9. 9SC Direzione Sanitaria, Ordine Mauriziano Hospital, 10028 Turin, Italy, Torino, Italy
  10. 10Gyn-Obst Unit, S. Croce e Carle Hospital, 12100 Cuneo, Italy, Cuneo, Italy
  11. 11Department of Oncology, University of Turin, 10124 Turin, Italy, Torino, Italy


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.

Disclosures None

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