Frontline maintenance treatment with selinexor resulted in a statistically significant improvement in median progression-free survival vs placebo in patients with advanced or recurrent endometrial cancer, meeting the primary end point of the phase 3 SIENDO trial.
Frontline maintenance treatment with selinexor (Xpovio) resulted in a statistically significant improvement in median progression-free survival (PFS) vs placebo in patients with advanced or recurrent endometrial cancer, meeting the primary end point of the phase 3 SIENDO (ENGOT-EN5/GOG-3055; NCT03555422) trial.1
Among 263 patients, the median PFS with the XPO1 inhibitor was 5.7 months vs 3.8 months with placebo, translating to an improvement of 50%, with a hazard ratio (HR) of 0.70 (P = .0486); this also represents a 30% reduction in the risk of disease progression or death in these patients.
Moreover, selinexor was found to produce sustained and long-term improvement, as was reported at 12 months, and investigators noted a 37% increase in the probability that those who received the agent would be in remission vs those without any treatment, who received the “watch-and-wait” approach.
Preliminary findings also revealed a prespecified subset of patients with wild-type p53 (n = 103) who experienced a significant 62% reduction in the risk of disease progression or death. Specifically, in this group, the median PFS with selinexor was 13.7 months vs just 3.7 months with placebo (HR, 0.38; P = .0006).
Regarding safety, no new safety signals were observed with selinexor. The agent was noted to be well tolerated, and to have a low toxicity-related treatment discontinuation rate of 10.5%.
“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 wilde-type p53,” Professor Ignace Vergote, MD, PhD, principal investigator and gynecologic oncologist, ENGOT and the Belgium and Luxembourg Gynaecological Oncology Group, University of Leuven, Leuven Cancer Institute, stated in a 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.”
The multicenter, blinded, placebo-controlled, phase 3 trial enrolled 263 patients with primary stage IV or recurrent endometrial cancer who achieved a partial or complete response following at least 12 weeks of standard taxane/platinum chemotherapy.
Eligibility criteria included being at least 18 years of age, an ECOG performance status of 0 or 1, and acceptable bone marrow function and organ function within 2 weeks prior to initiating the study drug, among other criteria.2
If patients had any sarcomas, small cell carcinoma with neuroendocrine differentiation, or clear cell carcinomas; received a blood or platelet transfusion in the 4 weeks before randomization; were receiving concurrent cancer treatment; previously received a XPO1 inhibitor, a PD-1/PD-L1 inhibitor, or concurrent treatment with an investigational agent in another trial; had active brain metastases; had known unstable cardiovascular function; or active hepatitis B and/or C infection, they were excluded from the trial.
Study participants were randomized 2:1 to receive either maintenance therapy with selinexor at a once-weekly dose of 80 mg, or 60 mg if body mass index was less than 20 kg/m2, or placebo. Treatment was administered until progressive disease.3
The primary end point of the trial was investigator-assessed PFS, and the goal of the research was to showcase a HR of 0.60 or better. Key secondary end points include PFS per blinded independent central review, disease-specific survival, overall survival, time to first subsequent treatment, PFS following subsequent treatment, time to second subsequent treatment, disease control rate, health-related quality of life, and treatment-emergent adverse effects.
“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, and member of GOG Foundation, Inc., added in the 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 heterogenous malignancy that is rising in incidence and disease-related mortality.”
Karyopharm Therapeutics, Inc., the drug developer, shared that they plan to work with investigators and the FDA to complete a full evaluation of the findings from SIENDO. Detailed data from the trial will be shared at an upcoming medical meeting in the first half of 2022.
The commercial-stage pharmaceutical company also announced plans to submit a supplemental new drug application for selinexor in this setting and population during the first half of 2022.