疗效显著：塞利尼索显著改善晚期或复发性子宫内膜癌的无进展生存期

Introduction: Seleniso can promote the nuclear storage and activation of tumor suppressor proteins and other growth regulatory proteins by inhibiting XPO1, and can reduce the levels of various oncogenic proteins in the cytoplasm, thereby arresting the tumor cell cycle and inducing apoptosis of tumor cells, while normal cells are not affected. Recently, studies have shown that the drug can significantly improve progression-free survival in advanced or recurrent endometrial cancer.

Results from the phase 3 SIENDO trial (NCT03555422) showed that frontline maintenance treatment with selinexor (Xpovio) significantly improved progression-free survival (PFS) in patients with advanced or recurrent endometrial cancer after combination with chemotherapy.

Developer Karyopharm Therapeutics has planned to work with the FDA to fully evaluate the study's results. In addition, the company will submit a supplemental new drug application to the FDA and present the study results at an upcoming medical meeting in the first half of 2022.

This global, multicenter, blinded, placebo-controlled, randomized study included 263 patients with primary stage IV or recurrent disease who had a partial or complete response after at least 12 weeks of statin/platinum-based chemotherapy. After chemotherapy, patients received 80 mg of selinesol or placebo weekly until disease progression.

Median PFS was 5.7 months for patients who received selinesol compared with 3.8 months for those who received placebo. Additionally, the risk of disease progression or death was reduced by 30%.

Other findings showed that the selinesol group produced long-term improvements at 12 months, as evidenced by a 37% increase in remission rates among patients treated with selinesol compared with placebo.

Preliminary data showed a significant 62% reduction in the risk of disease progression or death in a prespecified group of patients with p53 wild-type disease. In this group, median PFS was 13.7 months for patients who received selinesol versus 3.7 months for those who received placebo (HR, 0.38; P=0.0006).

No new safety findings emerged, and 10.5% of patients discontinued treatment due to adverse reactions.

"We are pleased to see a statistically significant improvement in PFS in the Phase 3 SIENDO study," said Sharon Shacham, Ph.D., chief scientific officer at Karyopharm. "If approved, selinesol will be the first and only maintenance therapy for patients with advanced or recurrent endometrial cancer after chemotherapy remission."

Principal investigator Dr. Ignace Vergote concluded: "As an oral, chemotherapy-free treatment, selinesol has the potential to change the way advanced or recurrent endometrial cancer is treated."

Previously, in July 2019, the FDA approved selinesol combined with low-dose dexamethasone for the treatment of patients with refractory relapsed multiple myeloma (rrMM).

In June 2020, the U.S. FDA once again approved selinesol as a monotherapy for patients with refractory relapsed diffuse large B-cell lymphoma (rrDLBCL).

In December 2020, the US FDA approved selinesol combined with bortezomib and dexamethasone for the treatment of multiple myeloma patients who have received at least one previous treatment regimen.

References:

https://www.cancernetwork.com/view/frontline-maintenance-selinexor-yields-significant-pfs-benefit-in-advanced-or-recurrent-endometrial-cancer