Publication details

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

Authors	MAKKER Vicky PEREZ-FIDALGO Jose Alejandro VALABREGA Giorgio HAMILTON Erika GORP Toon Van SEHOULI Jalid REGINÁČOVÁ Klaudia RICHARDSON Debra L PERRI Tamar OZA Amit M MILLER David S ALÍA Eva Maria Guerra GIORGI Ugo De HENRY Stephanie SPITZ Daniel L WIMBERGER Pauline BEDNAŘÍKOVÁ Markéta CHON Hye Sook MARTÍNEZ-GARCIA Jerónimo PISANO Carmela BEREK Jonathan S ROMERO Ignacio SCAMBIA Giovanni FARINAS-MADRID Lorena BUSCEMA Joseph SCHOCHTER Fabienne LI Kai KALYANAPU Pratheek WALKER Christopher J VERGOTE Ignace
Year of publication	2024
Type	Article in Periodical
Magazine / Source	Gynecologic Oncology
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://www.sciencedirect.com/science/article/pii/S0090825824002348?via%3Dihub
Doi	http://dx.doi.org/10.1016/j.ygyno.2024.05.016
Keywords	Cancer biomarker; Endometrial neoplasm; Exportin 1 proteinp; 53 tumor-suppressor protein
Description	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.