Selinexor Shows Statistically Significant Increase in Progression-Free Survival for Patients With Advanced, Recurrent Endometrial Cancer
Selinexor demonstrated a 37% increase in probability that patients treated with the drug will be in remission at 12 months.
Treatment with selinexor (Xpovio, Karyopharm) showed a statistically significant 50% improvement in median progression-free survival (PFS) among patients with advanced or recurrent endometrial cancer, according to results from the SIENDO study.
“We are thrilled to see a statistically significant improvement in median progression-free survival from the phase 3 SIENDO study because of what it represents for patients,” said Sharon Shacham, PhD, MBA, chief scientific officer of Karyopharm, in a press release. “If approved, Xpovio would be the first and only maintenance therapy in advanced or recurrent endometrial cancer, following response to chemotherapy.”
According to the press release, patients in the selinexor treatment arm had a median PFS of 5.7 months, compared to 3.8 months for patients receiving a placebo. This demonstrates an improvement of 50% with a hazard ratio of 0.70, representing a 30% reduction in the risk of disease progression or death. Selinexor also demonstrated a sustained and long-term improvement as seen at 12 months with a 37% increase in probability that patients treated with the drug will be in remission compared to patients on no treatment.
The SIENDO study is a global, multicenter, blinded, placebo-controlled, randomized phase 3 trial evaluating the efficacy and safety for front-line maintenance therapy with selinexor in patients with advanced or recurrent endometrial cancer. The study enrolled 263 patients with primary stage 4 or recurrent disease who had a partial or complete response after at least 12 weeks of standard taxane-platinum combination chemotherapy.
Participants were randomized 2:1 to receive either placebo or maintenance therapy of 80 mg of selinexor taken once weekly until disease progression. The primary endpoint is statistically significant improvement of PFS compared to placebo, with a hazard ratio of 0.6 or better, according to the press release.
“Women with advanced or recurrent endometrial cancer face a poor prognosis,” Vicky Makker, MD, principal investigator and medical oncologist at Memorial Sloan Kettering Cancer Center, said in the press release. “Following standard of care, platinum-based chemotherapy, the current paradigm of watchful waiting for recurrent 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.”
Karyopharm will work with FDA investigators to complete a full evaluation of data from the SIENDO trial, according to the press release. The preliminary data identified a pre-specified subgroup with wild-type p53, which achieved a statistically significant reduction in the risk of disease progression or death. In this group, patients treated with selinexor had a median PFS of 13.7 months compared to 3.7 months for patients receiving the placebo, representing a 62% reduction in the risk of disease progression or death.
According to the press release, inhibition of XPO1 by selinexor leads to the nuclear accumulation of p53, which is a well-established tumor suppressor protein. Based on these findings, Karyopharm plans to submit a supplemental New Drug Application to the FDA during the first half of 2022.
“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 Ignace Vergote, MD, said in the press release. “This study brings us one step closer to offering patients a treatment option that can give them more time with their friends and families.”
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. News release. Karyopharm Therapeutics; February 8, 2022. Accessed February 8, 2022. https://investors.karyopharm.com/2022-02-08-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?utm_campaign=press+release&utm_source=facebook,linkedin&utm_medium=social&utm_content=https://investors.karyoph