TY - JOUR
T1 - Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer
T2 - A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study
AU - Makker, Vicky
AU - Perez-Fidalgo, Jose Alejandro
AU - Valabrega, Giorgio
AU - Hamilton, Erika
AU - Van Gorp, Toon
AU - Sehouli, Jalid
AU - Regináčová, Klaudia
AU - Richardson, Debra L.
AU - Perri, Tamar
AU - Oza, Amit M.
AU - Miller, David S.
AU - Alía, Eva Maria Guerra
AU - De Giorgi, Ugo
AU - Henry, Stephanie
AU - Spitz, Daniel L.
AU - Wimberger, Pauline
AU - Bednaříková, Markéta
AU - Chon, Hye Sook
AU - Martínez-Garcia, Jerónimo
AU - Pisano, Carmela
AU - Berek, Jonathan S.
AU - Romero, Ignacio
AU - Scambia, Giovanni
AU - Fariñas-Madrid, Lorena
AU - Buscema, Joseph
AU - Schochter, Fabienne
AU - Li, Kai
AU - Kalyanapu, Pratheek
AU - Walker, Christopher J.
AU - Vergote, Ignace
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6
Y1 - 2024/6
N2 - 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).
AB - 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).
KW - Cancer biomarker
KW - Endometrial neoplasm
KW - Exportin 1 protein
KW - p53 tumor-suppressor protein
UR - http://www.scopus.com/inward/record.url?scp=85195102982&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2024.05.016
DO - 10.1016/j.ygyno.2024.05.016
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C2 - 38834399
AN - SCOPUS:85195102982
SN - 0090-8258
VL - 185
SP - 202
EP - 211
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -
