Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. / Vergote, I. B.; Lund, B.; Peen, U.; Umajuridze, Z.; Mau-Sorensen, M.; Kranich, A.; Van Nieuwenhuysen, E.; Haslund, C.; Nottrup, T.; Han, S. N.; Concin, N.; Unger, T. J.; Chai, Y.; Au, N.; Rashal, T.; Joshi, A.; Crochiere, M.; Landesman, Y.; Shah, J.; Shacham, S.; Kauffman, M.; Mirza, M. R.

I: Gynecologic Oncology, Bind 156, Nr. 2, 2020, s. 308-314.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Vergote, IB, Lund, B, Peen, U, Umajuridze, Z, Mau-Sorensen, M, Kranich, A, Van Nieuwenhuysen, E, Haslund, C, Nottrup, T, Han, SN, Concin, N, Unger, TJ, Chai, Y, Au, N, Rashal, T, Joshi, A, Crochiere, M, Landesman, Y, Shah, J, Shacham, S, Kauffman, M & Mirza, MR 2020, 'Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies', Gynecologic Oncology, bind 156, nr. 2, s. 308-314. https://doi.org/10.1016/j.ygyno.2019.11.012

APA

Vergote, I. B., Lund, B., Peen, U., Umajuridze, Z., Mau-Sorensen, M., Kranich, A., Van Nieuwenhuysen, E., Haslund, C., Nottrup, T., Han, S. N., Concin, N., Unger, T. J., Chai, Y., Au, N., Rashal, T., Joshi, A., Crochiere, M., Landesman, Y., Shah, J., ... Mirza, M. R. (2020). Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. Gynecologic Oncology, 156(2), 308-314. https://doi.org/10.1016/j.ygyno.2019.11.012

Vancouver

Vergote IB, Lund B, Peen U, Umajuridze Z, Mau-Sorensen M, Kranich A o.a. Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. Gynecologic Oncology. 2020;156(2):308-314. https://doi.org/10.1016/j.ygyno.2019.11.012

Author

Vergote, I. B. ; Lund, B. ; Peen, U. ; Umajuridze, Z. ; Mau-Sorensen, M. ; Kranich, A. ; Van Nieuwenhuysen, E. ; Haslund, C. ; Nottrup, T. ; Han, S. N. ; Concin, N. ; Unger, T. J. ; Chai, Y. ; Au, N. ; Rashal, T. ; Joshi, A. ; Crochiere, M. ; Landesman, Y. ; Shah, J. ; Shacham, S. ; Kauffman, M. ; Mirza, M. R. / Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. I: Gynecologic Oncology. 2020 ; Bind 156, Nr. 2. s. 308-314.

Bibtex

@article{b262480caa134ceda98a7691907a0b9d,
title = "Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies",
abstract = "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/m2 twice-weekly [BIW] or 50 mg/m2 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/m2 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.",
keywords = "Cervical cancer, Endometrial cancer, Ovarian cancer, Selinexor, XPO1",
author = "Vergote, {I. B.} and B. Lund and U. Peen and Z. Umajuridze and M. Mau-Sorensen and A. Kranich and {Van Nieuwenhuysen}, E. and C. Haslund and T. Nottrup and Han, {S. N.} and N. Concin and Unger, {T. J.} and Y. Chai and N. Au and T. Rashal and A. Joshi and M. Crochiere and Y. Landesman and J. Shah and S. Shacham and M. Kauffman and Mirza, {M. R.}",
year = "2020",
doi = "10.1016/j.ygyno.2019.11.012",
language = "English",
volume = "156",
pages = "308--314",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press",
number = "2",

}

RIS

TY - JOUR

T1 - Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies

AU - Vergote, I. B.

AU - Lund, B.

AU - Peen, U.

AU - Umajuridze, Z.

AU - Mau-Sorensen, M.

AU - Kranich, A.

AU - Van Nieuwenhuysen, E.

AU - Haslund, C.

AU - Nottrup, T.

AU - Han, S. N.

AU - Concin, N.

AU - Unger, T. J.

AU - Chai, Y.

AU - Au, N.

AU - Rashal, T.

AU - Joshi, A.

AU - Crochiere, M.

AU - Landesman, Y.

AU - Shah, J.

AU - Shacham, S.

AU - Kauffman, M.

AU - Mirza, M. R.

PY - 2020

Y1 - 2020

N2 - 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/m2 twice-weekly [BIW] or 50 mg/m2 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/m2 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.

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/m2 twice-weekly [BIW] or 50 mg/m2 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/m2 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.

KW - Cervical cancer

KW - Endometrial cancer

KW - Ovarian cancer

KW - Selinexor

KW - XPO1

U2 - 10.1016/j.ygyno.2019.11.012

DO - 10.1016/j.ygyno.2019.11.012

M3 - Journal article

C2 - 31822399

AN - SCOPUS:85076237672

VL - 156

SP - 308

EP - 314

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -

ID: 254462539