SIENDO phase III study: significant PFS benefits for endometrial patients with frontline maintenance selinexor treatment

According to a press release, the phase III SIENDO trial showed that treatment with frontline maintenance selinexor (Xpovio) after combination chemotherapy significantly improved the progression-free survival (PFS) of patients with advanced or recurrent endometrial cancer.

The global, multicenter, blinded, placebo-controlled, randomized SIENDO study enrolled 263 patients with primary stage IV or recurrent endometrial cancer. Only patients who had a partial or complete response following at least 12 weeks of treatment with taxane/platinum chemotherapy were included. Patients received 80 mg of selinexor weekly or placebo post-chemotherapy.  The study’s primary aim was to evaluate the efficacy and safety of frontline maintenance selinexor with combination chemotherapy. Treatment was continued until disease progression.

Main findings SIENDO

Treatment with selinexor significantly improved PFS compared to the placebo arm (5.7 vs 3.8 months, HR: 0.70; p=0.0486). Furthermore, a 30% reduction in risk of progression or death was observed. Also, the experimental therapy led to a 37% increase in the probability of remission among those treated with selinexor vs placebo.

The pre-specified group with p53 wild-type showed a significant reduction in risk of disease progression or death of 62%. Within this group, patients receiving selinxor had a median PFS of 13.7 months compared to 3.7 months with placebo (HR: 0.38; p=0.0006). No new treatment-related adverse effects were reported. Moreover, 10.5% of patients discontinued treatment due to the adverse impacts.

Conclusion

“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, PhD (gynecologic oncologist, ENGOT and Belgium and Luxembourg Gynaecological Oncology Group, University of Leuven, Leuven Cancer Institute) concluded. “This study brings us one step closer to offering patients a treatment option that can give them more time with their friends and families.”

Reference

1. 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.