Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies.
Adult
Aged
Aged, 80 and over
Cohort Studies
Female
Genital Neoplasms, Female
/ drug therapy
Humans
Hydrazines
/ administration & dosage
Karyopherins
/ antagonists & inhibitors
Middle Aged
Neoplasm Grading
Neoplasm Recurrence, Local
/ drug therapy
Progression-Free Survival
Receptors, Cytoplasmic and Nuclear
/ antagonists & inhibitors
Triazoles
/ administration & dosage
Exportin 1 Protein
Cervical cancer
Endometrial cancer
Ovarian cancer
Selinexor
XPO1
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
14
07
2019
revised:
24
10
2019
accepted:
08
11
2019
pubmed:
12
12
2019
medline:
6
5
2020
entrez:
12
12
2019
Statut:
ppublish
Résumé
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. In this phase 2 trial, patients received selinexor (35 or 50 mg/m 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 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.
Sections du résumé
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
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
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.
Identifiants
pubmed: 31822399
pii: S0090-8258(19)31663-4
doi: 10.1016/j.ygyno.2019.11.012
pii:
doi:
Substances chimiques
Hydrazines
0
Karyopherins
0
Receptors, Cytoplasmic and Nuclear
0
Triazoles
0
selinexor
31TZ62FO8F
Banques de données
ClinicalTrials.gov
['NCT02025985']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
308-314Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.