Sistema de Salut de Catalunya
Institut Català de la Salut
[Makker V] Memorial Sloan Kettering Cancer Center, New York, NY, USA. Weill Cornell Medical Center, New York, NY, USA. [Perez-Fidalgo JA] INCLIVA, CIBERONC, GEICO, Hospital Clinico Universitario de Valencia, Valencia, Spain. [Valabrega G] University of Turin, A.O. Ordine Mauriziano, Turin, Italy. [Hamilton E] Sarah Cannon Research Institute, Nashville, TN, USA. [Van Gorp T] Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. [Sehouli J] European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center, NOGGO, Charité–Berlin University of Medicine, Berlin, Germany. [Fariñas-Madrid L] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2024-06-14T08:12:55Z
2024-06-14T08:12:55Z
2024-06-03
Cancer biomarker; Endometrial neoplasm; P53 tumor-suppressor protein
Biomarcador de càncer; Neoplàsia endometrial; Proteïna supresora de tumors p53
Biomarcador de cáncer; Neoplasia endometrial; Proteína supresora de tumores p53
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).
This study was funded by Karyopharm Therapeutics Inc.
Article
Published version
English
Medicaments antineoplàstics - Ús terapèutic; Endometri - Càncer - Tractament; Avaluació de resultats (Assistència sanitària); DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Endometrial Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias endometriales; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos
Elsevier
Gynecologic Oncology;185
https://doi.org/10.1016/j.ygyno.2024.05.016
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
