Selinexor May Benefit Patients Ovarian or Endometrial Cancer

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Treatment with selinexor is active in patients with heavily pretreated patients with metastatic ovarian or endometrial cancer.
Treatment with selinexor is active in patients with heavily pretreated patients with metastatic ovarian or endometrial cancer.

Treatment with the oral selective inhibitor of nuclear export (SINE), selinexor, is active in patients with heavily pretreated patients with metastatic ovarian or endometrial cancer, according to preliminary data presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1

Nuclear export protein Exportin 1 (XPO1), which mediates the nuclear export of regulatory proteins, is expressive in aggressive ovarian cancers, and mutations in this protein are prevalent in patients with endometrial cancer. Researchers therefore assessed the efficacy and tolerability of selinexor among patients with metastatic gynecologic malignancies.

For the phase 2 SIGN trial (Phase II Study of KPT-330 (Selinexor) in Female Patients With Advanced Gynaecologic Malignancies & Metastatic Breast Cancer; ClinicalTrials.gov Identifier: NCT02025985), researchers enrolled 114 patients who had received at least 1 prior line of therapy. Of those, 66 had platinum-refractory/resistant ovarian cancer, 23 had relapsed endometrial cancer, and 25 had relapsed cervical cancer.

The disease control rate, which included complete response, partial responses, and stable disease for at least 12 weeks, was 49%, 43%, and 24% in patients with ovarian, endometrial, and cervical cancers, respectively.

Objective response rate was 14% in both the ovarian cancer and endometrial cancer groups, but was only 4% in the cervical cancer group.

Median progression-free survival was 11 weeks, 12 weeks, and 6 weeks in the ovarian, endometrial, and cervical cancer groups, respectively.

RELATED: Limiting Lynch Syndrome Screening in Endometrial Cancers May Be Harmful

The safety profile of selinexor was manageable in this treatment setting. The most common grade 3 to 4 treatment-related adverse events were thrombocytopenia, fatigue, anemia, and nausea.

Investigators are planning additional studies and phase 3 trials to further evaluate selinexor, both as a single-agent and in combination, in this patient population.                      

Reference

  1. Vergote I, Lund B, Havsteen H, et al. Results of a phase 2 trial of selinexor, an oral selective inhibitor of nuclear export (SINE) in 114 patients with gynaecological cancers. Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.

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