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 Journal Article
| Authors: | 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.; Pisano, C.; Berek, J. S.; Romero, I.; Scambia, G.; Fariñas-Madrid, L.; Buscema, J.; Schochter, F.; Li, K.; Kalyanapu, P.; Walker, C. J.; Vergote, I. |
| Article Title: | 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 |
| 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). © 2024 The Authors |
| Keywords: | adult; controlled study; aged; aged, 80 and over; middle aged; major clinical study; genetics; clinical trial; constipation; drug tolerability; fatigue; neutropenia; cancer recurrence; placebo; cancer combination chemotherapy; diarrhea; drug efficacy; drug safety; drug withdrawal; side effect; cancer patient; cancer staging; follow up; follow-up studies; endometrioid carcinoma; endometrial neoplasms; neoplasm staging; endometrium cancer; progression free survival; antineoplastic metal complex; neoplasm recurrence, local; anemia; nausea; randomized controlled trial; thrombocytopenia; vomiting; maintenance therapy; pathology; protein p53; abdominal pain; asthenia; cancer regression; multicenter study; tumor recurrence; mismatch repair; tumor suppressor protein p53; cataract; phase 3 clinical trial; taxane derivative; drug therapy; double blind procedure; tp53 protein, human; ileus; endometrium tumor; triazoles; triazole derivative; cancer biomarker; hydrazines; progression-free survival; decreased appetite; hydrazine derivative; procedures; general condition deterioration; maintenance chemotherapy; very elderly; humans; human; female; article; endometrial neoplasm; selinexor; exportin 1 protein; p53 tumor-suppressor protein |
| Journal Title: | Gynecologic Oncology |
| Volume: | 185 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-06-01 |
| Start Page: | 202 |
| End Page: | 211 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2024.05.016 |
| PUBMED: | 38834399 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
