Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study.

Makker, Vicky;Perez-Fidalgo, Jose Alejandro;Valabrega, Giorgio;Hamilton, Erika;Vergote, Ignace;et.al.
(2024) Gynecologic Oncology — Vol. 185, p. 202-211 (2024)

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Authors
  • Makker, Vicky
    Author
  • Perez-Fidalgo, Jose Alejandro
    Author
  • Valabrega, Giorgio
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  • Hamilton, Erika
    Author
  • Henry, StéphanieUCLouvain
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  • Vergote, Ignace
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Abstract
OBJECTIVE: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy. METHODS: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed. RESULTS: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified. CONCLUSION: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).
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Makker, V., Perez-Fidalgo, J. A., Valabrega, G., Hamilton, E., Van Gorp, T., Sehouli, J., Regináčová, K., Richardson, D. L., Perri, T., Oza, A. M., Miller, D. S., Alía, E. M. G., De Giorgi, U., Henry, S., Spitz, D. L., Wimberger, P., Bednaříková, M., Chon, H. S., Martínez-Garcia, J., et al. (2024). Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study. Gynecologic Oncology, 185, 202-211. https://doi.org/10.1016/j.ygyno.2024.05.016 (Original work published 2024)