PMID- 31822399 OWN - NLM STAT- MEDLINE DCOM- 20200505 LR - 20231213 IS - 1095-6859 (Electronic) IS - 0090-8258 (Linking) VI - 156 IP - 2 DP - 2020 Feb TI - Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. PG - 308-314 LID - S0090-8258(19)31663-4 [pii] LID - 10.1016/j.ygyno.2019.11.012 [doi] AB - BACKGROUND: Selinexor is an oral inhibitor of the nuclear export protein Exportin 1 (XPO1) with demonstrated antitumor activity in solid and hematological malignancies. We evaluated the efficacy and safety of selinexor in heavily pretreated, recurrent gynecological malignancies. METHODS: In this phase 2 trial, patients received selinexor (35 or 50 mg/m(2) twice-weekly [BIW] or 50 mg/m(2) once-weekly [QW]) in 4-week cycles. Primary endpoint was disease control rate (DCR) including complete response (CR), partial response (PR) or stable disease (SD) >/=12 weeks. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: 114 patients with ovarian (N = 66), endometrial (N = 23) or cervical (N = 25) cancer were enrolled. Median number of prior regimens for ovarian, endometrial and cervical cancer was 6 (1-11), 2 (1-5), and 3 (1-6) respectively. DCR was 30% (ovarian 30%; endometrial 35%; cervical 24%), which included confirmed PRs in 8%, 9%, and 4% of patients with ovarian, endometrial, and cervical cancer respectively. Median PFS and OS for patients with ovarian, endometrial and cervical cancer were 2.6, 2.8 and 1.4 months, and 7.3, 7.0, and 5.0 months, respectively. Common Grade 3/4 adverse events (AEs) were thrombocytopenia (17%), fatigue (14%), anemia (10%), nausea (9%) and hyponatremia (9%). Patients with ovarian cancer receiving 50 mg/m(2) QW had fewer high-grade AEs with similar efficacy as BIW treatment. CONCLUSIONS: Selinexor demonstrated single-agent activity and disease control in patients with heavily pretreated ovarian and endometrial cancers. Side effects were a function of dose level and treatment frequency, similar to previous reports, reversible and mitigated with supportive care. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Vergote, I B AU - Vergote IB AD - Department of Obstetrics and Gynaecology, Division of Gynecologic Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium, European Union. Electronic address: ignace.vergote@uzleuven.be. FAU - Lund, B AU - Lund B AD - Aalborg University Hospital, Aalborg, Denmark. FAU - Peen, U AU - Peen U AD - Herlev University Hospital, Herlev, Denmark. FAU - Umajuridze, Z AU - Umajuridze Z AD - Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Mau-Sorensen, M AU - Mau-Sorensen M AD - Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Kranich, A AU - Kranich A AD - GSO Hamburg, Germany. FAU - Van Nieuwenhuysen, E AU - Van Nieuwenhuysen E AD - Department of Obstetrics and Gynaecology, Division of Gynecologic Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium, European Union. FAU - Haslund, C AU - Haslund C AD - Aalborg University Hospital, Aalborg, Denmark. FAU - Nottrup, T AU - Nottrup T AD - Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Han, S N AU - Han SN AD - Department of Obstetrics and Gynaecology, Division of Gynecologic Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium, European Union. FAU - Concin, N AU - Concin N AD - Department of Obstetrics and Gynaecology, Division of Gynecologic Oncology, University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium, European Union. FAU - Unger, T J AU - Unger TJ AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Chai, Y AU - Chai Y AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Au, N AU - Au N AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Rashal, T AU - Rashal T AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Joshi, A AU - Joshi A AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Crochiere, M AU - Crochiere M AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Landesman, Y AU - Landesman Y AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Shah, J AU - Shah J AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Shacham, S AU - Shacham S AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Kauffman, M AU - Kauffman M AD - Karyopharm Therapeutics Newton, MA, USA. FAU - Mirza, M R AU - Mirza MR AD - Karyopharm Therapeutics Newton, MA, USA. LA - eng SI - ClinicalTrials.gov/NCT02025985 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191209 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (Hydrazines) RN - 0 (Karyopherins) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Triazoles) RN - 31TZ62FO8F (selinexor) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cohort Studies MH - Female MH - Genital Neoplasms, Female/*drug therapy/metabolism/pathology MH - Humans MH - Hydrazines/*administration & dosage/adverse effects MH - Karyopherins/*antagonists & inhibitors/metabolism MH - Middle Aged MH - Neoplasm Grading MH - Neoplasm Recurrence, Local/*drug therapy/pathology MH - Progression-Free Survival MH - Receptors, Cytoplasmic and Nuclear/*antagonists & inhibitors/metabolism MH - Triazoles/*administration & dosage/adverse effects MH - Exportin 1 Protein OTO - NOTNLM OT - Cervical cancer OT - Endometrial cancer OT - Ovarian cancer OT - Selinexor OT - XPO1 EDAT- 2019/12/12 06:00 MHDA- 2020/05/06 06:00 CRDT- 2019/12/12 06:00 PHST- 2019/07/14 00:00 [received] PHST- 2019/10/24 00:00 [revised] PHST- 2019/11/08 00:00 [accepted] PHST- 2019/12/12 06:00 [pubmed] PHST- 2020/05/06 06:00 [medline] PHST- 2019/12/12 06:00 [entrez] AID - S0090-8258(19)31663-4 [pii] AID - 10.1016/j.ygyno.2019.11.012 [doi] PST - ppublish SO - Gynecol Oncol. 2020 Feb;156(2):308-314. doi: 10.1016/j.ygyno.2019.11.012. Epub 2019 Dec 9.