Article Text

Download PDFPDF

#264 Long-term follow up of selinexor maintenance for patients with TP53wt advanced or recurrent endometrial cancer: a pre-specified subgroup analysis from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study
  1. Alejandro Pérez Fidalgo1,
  2. Ignace Vergote2,
  3. Erika Hamilton3,
  4. Giorgio Valabrega4,
  5. Toon Van Gorp5,
  6. Jalid Sehouli6,
  7. Jaroslav Klat7,
  8. Tally Levy8,
  9. Stephen Welch9,
  10. Debra L Richardson10,
  11. Eva Maria Guerra Alía11,
  12. Giovanni Scambia12,
  13. Stéphanie Henry13,
  14. Pauline Wimberger14,
  15. David Miller15,
  16. Jerónimo Martínez16,
  17. Bradley J Monk17,
  18. Pratheek Kalyanapu18,
  19. Mansoor Raza Mirza19 and
  20. Vicky Makker20
  1. 1GEICO. Hospital Clinico Universitario de Valencia. INCLIVA. CIBERONC, Valencia, Spain
  2. 2BGOG and Leuven Cancer Institute, University Hospitals Leuven,, Leuven, Belgium
  3. 3Sarah Cannon Research Institute, Tennesee Oncology, Nashville, United States
  4. 4MITO and Department of Oncology, University of Torino, at Mauriziano Hospital, Turin, Italy
  5. 5BGOG and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
  6. 6NOGGO and Department of Gynecology, European Competence Center for Ovarian Cancer, Charité Comprehensive Cancer Center, Charité–Berlin University of Medicine, Berlin, Germany
  7. 7CEEGOG and University Hospital Ostrava and University of Ostrava, Ostrava-Poruba, Czech Republic
  8. 8ISGO and Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  9. 9London Health Sciences Centre, London, United Kingdom
  10. 10Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, United States
  11. 11GEICO and Hospital Universitario Ramón y Cajal, Madrid, Spain
  12. 12MITO and Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  13. 13BGOG and Université Catholique de Louvain, CHU UCL Namur Site Ste Elisabeth, Service d’onco-hématologie (SORMN),, Namur, Belgium
  14. 14NOGGO and Technische Universitat Dresden, University Hospital Carl Gustav Carus
  15. 15Department of Obstetrics and Gynecology, Dresden, GermanyDepartment of Obstetrics and Gynecology, University of Texas Southwestern Medical Center; Harold C. Simmons Comprehensive Cancer Center, Dallas, United States
  16. 16GEICO and Hospital Universitario Virgen de la Arrixaca, Department of Oncology, Murica, Spain
  17. 17GOG Foundation, University of Arizona, Creighton University, Phoenix, United States
  18. 18Karyopharm Therapeutics, Newton, United States
  19. 19Rigshospitalet – Copenhagen University Hospital, Copenhagen, Denmark
  20. 20Memorial Sloan Kettering Cancer Center, New York, United States


Introduction/Background Molecular characterization is important to inform treatment decisions for patients with endometrial cancer (EC). Wild type TP53 (TP53wt) is found in ~75% of newly diagnosed EC and 50% of advanced/recurrent tumors; there are no specific targeted therapies for patients with TP53wt EC. Selinexor is an investigational oral XPO1 inhibitor that drives nuclear retention and functional activation of wt tumor suppressor proteins, including p53.

Methodology SIENDO (NCT03555422) was a phase 3 double-blind study evaluating selinexor vs placebo as maintenance in patients with advanced/recurrent EC. The primary endpoint was progression-free survival (PFS) and first presented at the ESMO plenary in March 2022. Selinexor efficacy and safety was now further assessed with long-term follow-up in a prespecified subgroup of patients with TP53wt EC.

Results 113 patients with TP53wt EC were randomized (selinexor, n=77/placebo, n=36). As of data cutoff on Nov 30, 2022, median follow-up was 20.3 months, with 26.3% and 22.9% patients still on selinexor and placebo treatment, respectively. Median PFS for TP53wt subgroup was 20.8 months with selinexor vs 5.2 months with placebo (HR [Stratified by chemotherapy response CR vs PR] 0.46; 95% CI (0.27, 0.79), nominal one-sided p-value=0.0020). The most common adverse events (AEs) of any grade (selinexor/placebo) were nausea (90%/34%), vomiting (61%/11%) and diarrhea (38%/34%); and most common grade 3+ AEs: neutropenia (18%/0%), nausea (12%/0%), and thrombocytopenia (9%/0%). TEAEs leading to discontinuations occurred at a rate of 15%/0%.

Conclusion Long-term follow-up of a pre-specified subgroup analysis showed durable PFS with selinexor maintenance in TP53wt EC, which offers the potential to prolong prior chemotherapy response. These data suggest that TP53 status is a robust prognostic biomarker for EC and selinexor may provide meaningful benefits for these patients. Updated data will be presented. A phase 3 trial of selinexor as a maintenance therapy in TP53wt EC is underway (NCT05611931).

Disclosures Ignace Vergote has received grants/research support from Oncoinvent AS (2019–2020) GRANT = CORPORATE SPONSORED RESEARCH -Amgen (2019–2020) -Roche (2019–2020); received honoraria or consulting fees from Agenus (2021) - Aksebio (2021) - Amgen (Europe) GmbH (2019) - AstraZeneca (2019–2022) - Bristol Myers Squibb (2021) - Clovis Oncology Inc. (2019–2019) -Carrick Therapeutics (2019) - Deciphera Pharmaceutials; and Accommodations, travel expenses (2019–2020) -

Amgen - MSD - Tesaro - AstraZeneca - Roche. Alejandro Pérez Fidalgo has received grants/research supports from Pharmamar and GSK (my institution); Participation in a company sponsored speaker’s bureau Astrazeneca, GSK, Clovis, Pharmamar (myself); and honoraria or consultation fees GSK, Clovis, Astrazeneca, Pharmamar, Roche. Erika Hamilton has received grants/research supports from (Made to institution) Abbvie Acerta Pharma ADC Therapeutics AKESOBIO Australia Amgen Aravive ArQule Arvinas AstraZeneca AtlasMedx Black Diamond Boehringer Ingelheim Clovis Compugen Curis CytomX Daiichi Sankyo Dana Farber Cancer Inst Deciphera eFFECTOR Therapeutics Ellipses Pharma EMD Serono Fochon FujiFilm G1 Therapeutics H3 Biomedicine Harpoon Hutchinson MediPharma Immunogen Immunomedics Incyte InvestisBio Jacobio Karyopharm Leap Therapeutics Lilly Lycera Mabspace Biosciences Macrogenics MedImmune Merck Mersana Merus Millennium Molecular Templates Myraid Genetic Laboratories Novartis Nucana Olema OncoMed Onconova Therapeutics ORIC Pharmaceuticals Orinove Pfizer PharmaMar Pieris Pharmaceuticals Pionyr Immunotherapeutics Plexxikon Radius Health Regeneron Repertoire Immune Medicine Rgenix Roche/Genentech Seattle Genetics Sermonix Pharmaceuticals Shattuck Labs Silverback StemCentRx Sutro Syndax Syros Taiho TapImmune Tesaro Treadwell Therapeutics Verastem Vincerx Pharma Zenith Epigenetics Zymeworks; and Consulting/Advisory role (made to institution) : Arcus Arvinas AstraZeneca Black Diamond Boehringer Ingelheim CytomX Daiichi Sankyo Dantari Deciphera Pharmaceuticals Eisai H3 Biomedicine iTeos Janssen Lilly Loxo Merck Mersana Novartis Pfizer Puma Biotechnology Relay Therapeutics Roche/Genentech Seattle Genetics Silverback Therapeutics. Giorgio Valabrega has received consulting or advisory fee from GSK, PharmaMar, astrezeneca, MSD, and Eisai. Toon Van Gorp has received grants/research supports fromAmgen,

AstraZeneca, Roche; Advisory board (all payed to institute): AstraZeneca, Eisai, GSK, ImmunoGen, MSD, OncXerna, Seagen, Tubulis; Participation in a company sponsored speaker’s bureau GSK. Jalid Sehouli has Advisory Board, Personal, Invited Speaker GSK, MSD,

PharmaMar, novocure, Tesaro, Astra Zeneca, Clovis, Eisei, Roche, Merck, Bayer, Molecular Health, Riemser instutional: Karyopharm, GSK, Astra Zeneca, Clovis, MSD, PharmaMar, Novartis, Tesaro, Novocure, MSD, Eisei, Roche Diagnostics, Molecular Health, Riemser. Jaroslav Klat has no conflicts of interest to disclose. Tally Levy has no conflicts of interest to disclose. Stephen Welch has received Honoraria: Roche Canada, GSK, Pfizer, Eisai, Merck. Consulting or advisory role: Amgen, Eisai. Debra L Richardson has received fees for Advisory Board: Mersana, GlaxoSmithKline. Advisory board participant and moderator: AstraZeneca. Eva Maria Guerra Alía has received fees for Advisory/consultancy: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; Speaker bureau/expert testimony: AstraZeneca, PharmaMar, Roche, GSK; and Travel/accommodation/expenses: Roche, TESARO: A GSK Company and Baxter. Giovanni Scambia has received fees for grants/research supports from MSD Italia S.r.l.; Consultant: TESARO Bio Italy S.r.l. Johnson & Johnson; and Speakers Bureau/Honoraria: Clovis Oncology Italy S.r.l.. Stéphanie Henry has received fees for honoraria or consultation AstraZeneca, Merck, Novartic, MSD Oncology, BMSi, Sanofi, Gelead, GSK; and Travel, Accommodations, Expenses: Roche, MSD, GSK, Teva. Pauline Wimberger has received fees for Honoraria, Astrazeneca, MSD, Eisai, Novartis, Roche, Amgen, Pfizer Clovis, Gilead, Lilly. Consulting or advisory role, Astrazeneca, MSD, Eisai, Novartis, Pfizer, Roche, Amgen, Clovis, Lilly, Gilead, GSK. Funded research, Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche, GSK, Clovis. David Miller has received fees for Consulting or adisory: genentech, Tesaro, Eisai, AstraZeneca, Guardant Health, Janssen Oncology, Karyopharm Therapeutics, Incyte, Janssen, Alexion Pharmaceuticals, Clovis Oncology, Asymmetric Therapeutics, LLC, Boston Biomedical, Research Institute, Tarveda Therapeutics, Myriad Genetic Laboratories Inc, GlaxoSmithKline LLC, AbbiVie Inc, EMD Serono Inc, Seagen Inc, Clinical Education Alliance LLC, Eisai Europe Limited, iTeos Belgium SA, Novocure Inc, Novartis. Jerónimo Martínez has received fees for Advisory/consultancy honorarium from AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar; Speaker bureau/expert testimony honorarium from PharmaMar, GSK-Tesaro, Clovis; and Travel/accommodation/expenses from PharmaMar, GSK-Tesaro. Bradley J Monk has received honorarium and consulting fees from

Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna Health Care,

Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL, Verastem, Zentalis; and Speaker/Consultant AstraZeneca, Clovis, Easai, Merck, Roche/Genentech, TESARO/GSK. Giorgio Valabrega has received Consulting or advisory: GSK, PharmaMar, Astrazeneca, MSD. Pratheek Kalyanapu is an employee of Karyopharm Therapeutics. Mansoor Raza Mirza has received grants/research supports from AstraZeneca (Inst); Boehringer Ingelheim (Inst); Pfizer (Inst); Tesaro (Inst); honoraria or consultation fees from Honoraria - Advaxis; AstraZeneca; Cerulean Pharma; Clovis Oncology; Novocure; Pfizer; Roche; tesaro Consulting or Advisory Role - AstraZeneca; BioCad; Cerulean Pharma; Clovis Oncology; Genmab; Karyopharm Therapeutics; Novocure; Pfizer; Tesaro; Stock shareholder Karyopharm Therapeutics; SeraCare; and Leadership - Karyopharm Therapeutics;

SeraCare; Travel Accommodations AstraZeneca; Karyopharm Therapeutics; Pfizer; Roche; SeraCare; Tesaro. Vicky Makker has received grants/research supports (Funding to institution) NIH/NCI Cancer Center Support Grant (P30 CA008748); and unpaid consultancy/unpaid advisory board membership from AstraZeneca, Clovis, Eisai, Faeth, Genentech, GSK, iTEOS, Novartis, Karyopharm, Moreo, MSD, Takeda, and Zymeworks.

© 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.