- Selinexor maintenance shows durable clinical benefit in endometrial cancer.
- Significant PFS improvement over placebo in TP53 wild-type patients.
- Safety profile of selinexor indicates manageable adverse effects in treatment.
Selinexor Proves Durable in Clinical Study After Chemotherapy
Selinexor Maintenance In Advanced Endometrial Cancer Shows Solid Outcomes Data presented at the 2025 ESMO Gynecological Cancers Congress highlights the positive impact of selinexor (Xpovio) maintenance therapy on patients with TP53 wild-type advanced or recurrent endometrial cancer. In a long-term follow-up from the phase 3 SIENDO trial (NCT03555422), the findings underscore a durable clinical benefit as measured by progression-free survival (PFS), time to first subsequent therapy (TFST), and other key metrics compared to placebo. Notably, out of 263 patients evaluated, over 43% had TP53 wild-type disease, receiving either selinexor or placebo, which enhances our understanding of the drug’s efficacy within varying subgroup responses.
Safety Considerations and Treatment Efficacy Observed
In terms of progression-free survival, the results were striking. In the TP53 wild-type/mismatch repair-proficient (pMMR) subgroup, those undergoing treatment with selinexor had a median PFS of 39.5 months, a stark contrast to just 4.9 months with placebo. Meanwhile, the TP53 wild-type/MMR-deficient (dMMR) subgroup showed median PFS of 13.1 months against 3.7 months respectively. Highlights of the study also revealed consistent improvements across TFST and time to second progression (PFS2), reinforcing the cumulative effectiveness of selinexor without hindering subsequent therapies like immunotherapy, as reported by Dr. J. Alejandro Pérez Fidalgo and colleagues.
Future Directions in Therapy for Endometrial Cancer
As for safety, the adverse effects profile of selinexor was notable. Out of 76 patients treated, 90% reported nausea, followed by 60% experiencing vomiting, and 45% diarrhea. Serious grade 3 or higher treatment-emergent adverse effects (TEAEs) included neutropenia (20%) and thrombocytopenia (10%), though overall, these were less frequent in comparison to placebo. Only 16% of selinexor patients had TEAEs leading to treatment discontinuation, in contrast with no such reports within the placebo group. Moving forward, ongoing studies such as the phase 3 XPORT-EC trial aim to continue exploring selinexor’s role in advanced endometrial cancer therapy, offering hope for further advances in treatment.
In summary, the long-term follow-up data from the SIENDO trial reveals that selinexor maintenance therapy demonstrates significant benefits for patients with TP53 wild-type advanced or recurrent endometrial cancer. The therapy continues to provide durable outcomes such as improved PFS and TFST without compromising subsequent treatment options. As research progresses, the XPORT-EC trial will further evaluate the potential of selinexor, paving the way for enhanced management strategies in a challenging condition.
