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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

V. Makker, JA. Perez-Fidalgo, G. Valabrega, E. Hamilton, T. Van Gorp, J. Sehouli, K. Regináčová, DL. Richardson, T. Perri, AM. Oza, DS. Miller, EMG. Alía, U. De Giorgi, S. Henry, DL. Spitz, P. Wimberger, M. Bednaříková, HS. Chon, J....

. 2024 ; 185 (-) : 202-211. [pub] 20240603

Language English Country United States

Document type Journal Article, Clinical Trial, Phase III, Randomized Controlled Trial, Multicenter Study

Persistent link   https://www.medvik.cz/link/bmc24013605

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).

Arizona Oncology Tucson AZ USA

Belgium and Luxembourg Gynaecological Oncology Group Leuven Cancer Institute University Hospitals Leuven Leuven Belgium

Belgium and Luxembourg Gynaecological Oncology Group Namur Belgium

Charles University 3rd Faculty of Medicine Prague Czech Republic

Department of Oncology University Hospital Kralovske Vinohrady Prague Czech Republic

European Competence Center for Ovarian Cancer Charité Comprehensive Cancer Center NOGGO Charité Berlin University of Medicine Berlin Germany

Florida Cancer Specialists and Research Institute Wellington FL USA

Fondazione Policlinico Universitario A Gemelli IRCCS Rome 00168 Italy

Hadassah Medical Center Hebrew University of Jerusalem Jerusalem Israel

Harold C Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center Dallas TX USA

Hospital Clínico Universitario Virgen de la Arrixaca IMIB ARRIXACA Murcia Spain

Hospital Universitario Ramón y Cajal Madrid Spain

INCLIVA CIBERONC GEICO Hospital Clinico Universitario de Valencia Valencia Spain

IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori Meldola Italy

Istituto Nazionale Tumori di Napoli Naples Italy

Karyopharm Therapeutics Inc Newton MA USA

Memorial Sloan Kettering Cancer Center New York NY USA

Moffitt Cancer Center Tampa FL USA

Princess Margaret Cancer Centre University Health Network University of Toronto Toronto ON Canada

Sarah Cannon Research Institute Nashville TN USA

Stanford Women's Cancer Center Stanford Cancer Institute University School of Medicine Stanford CA USA

Stephenson Cancer Center University of Oklahoma Health Sciences Center Oklahoma City OK USA

Università Cattolica del Sacro Cuore Rome 00168 Italy

University Hospital and Masaryk University Brno Prague Czech Republic

University Hospital Carl Gustav Carus NOGGO and Technische Universität Dresden Dresden Germany

University Hospital Ulm Ulm Germany

University of Turin A O Ordine Mauriziano Turin Italy

Vall d'Hebron Universitiy Hospital Vall d'Hebron Institute of Oncology Barcelona Spain

Weill Cornell Medical Center New York NY USA

References provided by Crossref.org

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$a 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 / $c V. Makker, JA. Perez-Fidalgo, G. Valabrega, E. Hamilton, T. Van Gorp, J. Sehouli, K. Regináčová, DL. Richardson, T. Perri, AM. Oza, DS. Miller, EMG. Alía, U. De Giorgi, S. Henry, DL. Spitz, P. Wimberger, M. Bednaříková, HS. Chon, J. Martínez-Garcia, C. Pisano, JS. Berek, I. Romero, G. Scambia, L. Fariñas-Madrid, J. Buscema, F. Schochter, K. Li, P. Kalyanapu, CJ. Walker, I. Vergote
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$a 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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