Selinexor Improves Progression-Free Survival in Advanced Endometrial Cancer

Selinexor, an oral selective inhibitor of nuclear export, demonstrated promising efficacy in increasing progression-free survival among women with advanced endometrial cancer.

Selinexor (Xpovio) led to an improvement in progression-free survival (PFS) compared with placebo in women with advanced or recurrent endometrial cancer, according to findings from the phase 3 SIENDO trial (NCT03555422).1 In addition, the oral agent was associated with manageable toxicity and a relatively low discontinuation rate.

Results showed that the median PFS was 5.7 months with selinexor compared with 3.8 months with placebo, which translated to a 30% reduced risk of disease progression or death (HR, 0.70; P = .0486). In total, 10.5% of patients who received selinexor discontinued due to adverse events (AEs).

Full findings of SIENDO will be presented at an upcoming medical meeting in the first half of 2022.

"Women with advanced or recurrent endometrial cancer face a poor prognosis," principal investigator Vicky Makker, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, stated in a press release. "Following standard of care, platinum-based chemotherapy, the current paradigm of watchful waiting for recurrence is simply inadequate. Therefore, there is a dire need for new and innovative treatment options for this heterogeneous malignancy that is rising in incidence and disease-related mortality."

Selinexor is a selective inhibitor of nuclear exports (SINE) and functions by binding to and therefore inhibiting the nuclear export protein of XPO1.

In the multicenter, blinded, placebo-controlled, randomized phase 3 SIENDO study, investigators enrolled 236 patients with stage IV or recurrent endometrial cancer who had achieved either a partial or complete response following 12 weeks of standard treatment with taxane-platinum combination chemotherapy. After enrollment, participants were randomized 1:1 to receive either selinexor maintenance therapy at 80 mg once weekly, or placebo, until disease progression.

The trial met its primary end point of statistically significant improvement in PFS compared with placebo, with a goal of an HR of 0.6 or better.

Additional data showed that patients who had p53 wild-type disease (n = 103) also achieved a statistically significant reduction in disease progression or death (HR, 0.38; P = .0006). The median PFS was 13.7 months with selinexor vs 3.7 months with placebo.

Important AEs to remain aware of when administering this agent to patients include thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, embryo-fetal toxicity, and cataracts. Patients with multiple myeloma or diffuse large B-cell lymphoma (DLBCL) have also commonly reported fatigue, nausea, decreased appetite, diarrhea, anemia, constipation, and laboratory abnormalities.

"As an oral, chemotherapy-free treatment, selinexor has the potential to transform the way advanced or recurrent endometrial cancer is treated and I am intrigued to learn more about the patients with the wild-type p53," principal investigator Professor Ignace Vergote, principal investigator and gynecologist oncologist, ENGOT and the Belgium and Luxembourg Gynaecological Oncology Group (BGOG), University of Leuven, Leuven Cancer Institute in Leuven, Belgium, stated. "This study brings us one step closer to offering patients a treatment option that can give them more time with their friends and families."

Selinexor is currently approved by the FDA for use in combination with bortezomib (Velcade) and dexamethasone in patients with multiple myeloma after at least 1 prior therapy, in combination with dexamethasone in patients with heavily pretreated multiple myeloma, and for use in patients with DLBCL, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.

Reference

Karyopharm Announces Phase 3 SIENDO Study Meets Primary Endpoint with Statistically Significant Increase in Progression-Free Survival in Patients with Advanced or Recurrent Endometrial Cancer. Karyopharm. News release. February 8, 2022. Accessed February 17, 2022. https://bit.ly/3sL2CFj