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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

Makker, Vicky
Author Makker, Vicky Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical Center, New York, NY, USA
Perez-Fidalgo, Jose Alejandro
Author Perez-Fidalgo, Jose Alejandro INCLIVA, CIBERONC, GEICO, Hospital Clinico Universitario de Valencia, Valencia, Spain
Valabrega, Giorgio
Author Valabrega, Giorgio University of Turin, A.O. Ordine Mauriziano, Turin, Italy
Hamilton, Erika
Author Hamilton, Erika Sarah Cannon Research Institute, Nashville, TN, USA
Van Gorp, Toon
Author Van Gorp, Toon Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
Sehouli, Jalid
Author Sehouli, Jalid European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center, NOGGO, Charité-Berlin University of Medicine, Berlin, Germany
Regináčová, Klaudia
Author Regináčová, Klaudia Department of Oncology, University Hospital Kralovske Vinohrady, Prague, Czech Republic; Charles University, Third Faculty of Medicine, Prague, Czech Republic
Richardson, Debra L
Author Richardson, Debra L Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Perri, Tamar
Author Perri, Tamar Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
Oza, Amit M
Author Oza, Amit M Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada
Miller, David S
Author Miller, David S Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
Alía, Eva Maria Guerra
Author Alía, Eva Maria Guerra Hospital Universitario Ramón y Cajal, Madrid, Spain
De Giorgi, Ugo
Author De Giorgi, Ugo IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy
Henry, Stephanie
Author Henry, Stephanie Belgium and Luxembourg Gynaecological Oncology Group (BGOG) and Université Catholique de Louvain CHU UCL Site Ste Elisabeth, Service d'onco-hématologie (SORMIN), Namur, Belgium
Spitz, Daniel L
Author Spitz, Daniel L Sarah Cannon Research Institute, Nashville, TN, USA; Florida Cancer Specialists & Research Institute, Wellington, FL, USA
Wimberger, Pauline
Author Wimberger, Pauline University Hospital Carl Gustav Carus, NOGGO, and Technische Universität Dresden, Dresden, Germany
Bednaříková, Markéta
Author Bednaříková, Markéta University Hospital and Masaryk University, Brno, Prague, Czech Republic; Charles University, Third Faculty of Medicine, Prague, Czech Republic
Chon, Hye Sook
Author Chon, Hye Sook Moffitt Cancer Center, Tampa, FL, USA
Martínez-Garcia, Jerónimo
Author Martínez-Garcia, Jerónimo Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-ARRIXACA, Murcia, Spain
Pisano, Carmela
Author Pisano, Carmela Istituto Nazionale Tumori di Napoli, Naples, Italy
Berek, Jonathan S
Author Berek, Jonathan S Stanford Women's Cancer Center, Stanford Cancer Institute, University School of Medicine, Stanford, CA, USA
Romero, Ignacio
Author Romero, Ignacio INCLIVA, CIBERONC, GEICO, Hospital Clinico Universitario de Valencia, Valencia, Spain
Scambia, Giovanni
Author Scambia, Giovanni Università Cattolica del Sacro Cuore, Rome 00168, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome 00168, Italy
Fariñas-Madrid, Lorena
Author Fariñas-Madrid, Lorena Vall d'Hebron Universitiy Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain
Buscema, Joseph
Author Buscema, Joseph Arizona Oncology, Tucson, AZ, USA
Schochter, Fabienne
Author Schochter, Fabienne University Hospital Ulm, Ulm, Germany
Li, Kai
Author Li, Kai Karyopharm Therapeutics Inc., Newton, MA, USA
Kalyanapu, Pratheek
Author Kalyanapu, Pratheek Karyopharm Therapeutics Inc., Newton, MA, USA
Walker, Christopher J
Author Walker, Christopher J Karyopharm Therapeutics Inc., Newton, MA, USA
Vergote, Ignace
Author Vergote, Ignace Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. Electronic address: Ignace.vergote@uzleuven.be

Gynecologic oncology. 2024 Jun ; 185 () : 202-211. [epub] 20240603

Gynecol Oncol
ISSN 1095-6859 | 0090-8258
Source

Language English Country United States Media print-electronic

Document type Journal Article, Clinical Trial, Phase III, Randomized Controlled Trial, Multicenter Study, Research Support, Non-U.S. Gov't

Persistent link https://www.medvik.cz/link/pmid38834399

Grant support
P30 CA142543 NCI NIH HHS - United States

PubMed 38834399
DOI 10.1016/j.ygyno.2024.05.016
PII: S0090-8258(24)00234-8
Knihovny.cz E-resources

Keywords
Cancer biomarker, Endometrial neoplasm, Exportin 1 protein, p53 tumor-suppressor protein,
MeSH
Progression-Free Survival MeSH
Adult MeSH
Hydrazines * adverse effects administration & dosage therapeutic use MeSH
Middle Aged MeSH
Humans MeSH
Neoplasm Recurrence, Local * drug therapy MeSH
Tumor Suppressor Protein p53 * genetics MeSH
Endometrial Neoplasms * drug therapy genetics pathology MeSH
Follow-Up Studies MeSH
Aged, 80 and over MeSH
Aged MeSH
Neoplasm Staging MeSH
Triazoles * administration & dosage adverse effects therapeutic use MeSH
Maintenance Chemotherapy methods MeSH
Check Tag
Adult MeSH
Middle Aged MeSH
Humans MeSH
Aged, 80 and over MeSH
Aged MeSH
Female MeSH
Publication type
Journal Article MeSH
Clinical Trial, Phase III MeSH
Multicenter Study MeSH
Research Support, Non-U.S. Gov't MeSH
Randomized Controlled Trial MeSH
Names of Substances
Hydrazines * MeSH
Tumor Suppressor Protein p53 * MeSH
selinexor MeSH Browser
TP53 protein, human MeSH Browser
Triazoles * MeSH

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

Department of Oncology University Hospital Kralovske Vinohrady Prague Czech Republic; Charles University 3rd Faculty of Medicine Prague Czech Republic

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

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