Exploring Selinexor’s Efficacy in P53-Mutated Endometrial Cancer: Insights from Recent Clinical Trials

Selinexor (XPOVIO®) is an anti-cancer drug used in the treatment of various malignant conditions including a condition called refractory multiple myeloma. This is multiple myeloma that is not responsive to treatment or rapidly progresses within 60 days of therapy.

selinexor

Selinexor

It is a selective inhibitor of nuclear export and it functions by binding to exportin 1 (XPO1), which is a protein found in the nucleus of cancer cells, leading to the trapping of cancer cell suppressors in the nucleus. Subsequently, the trapped tumor suppressors cause cell growth arrest and death by a process called apoptosis.

Selinexor was approved by the U.S. Food and Drug Administration in 2019, following several studies which provided tangible evidence of its safety and effectiveness in targeting the nuclear transport of cancer cells.

It was further approved for use to treat refractory diffuse large B-cell lymphoma (DLBCL) and multiple myeloma in combination with dexamethasone and bortezomib.

A clinical trial called the EN5/GOG-3055/SIENDO or simply, the SIENDO study, is currently ongoing to assess the effectiveness of selinexor on the treatment and the degree of progression-free survival (PFS) of people with endometrial cancer that are positive for the p53 gene.

Progression-free survival is the amount of time between the onset of administration of a therapy and the time the disease condition gets worse. The SIENDO study set out to determine this time frame after the administration of selenixor.

Selinexor shows longer duration of PFS

Approximately a quarter of people with recurrent or advanced endometrial cancer have an altered p53 which is mainly caused by a missense mutation. P53 mutations have been detected in roughly 90% of people with type 2 endometrial cancer.

The SIENDO study is a randomized control interventional study currently in its 3rd phase. It tested Selinexor as a maintenance therapy in people with type 2 endometrial cancer with altered p53.

Recent reports presented as part of the July 2023 session of the American Society of Clinical Oncology (ASCO) Plenary Series, reveal that the data obtained so far were surprisingly unexpected.

They recruited 263 female participants, 18 years and above, who had been on taxane-platinum combination therapy and had been in total or partial remission. Participants received 80mg of the intervention drug, Selinexor, and a matching placebo.

Results posted in the Annals of Oncology showed that after an average follow-up period of 10.2 months, the PFS was approximately 5.7 months with Selinexor and 3.8 months with placebo. A subgroup analysis done, after an average follow-up period of 20.3 months, showed a PFS value of 20.8 months with Selinexor and 5.2 months with placebo.

Side effects of selinexor administration include nausea, vomiting, diarrhea, neutropenia, and thrombocytopenia.

Clinical significance

The reports show that selinexor increases the duration of progression-free survival and it offers an extended response to previous systemic drug therapy. It also confirms that p53 mutation is the key factor in type 2 endometrial cancer and that Selinexor is effective in patients who have this kind of tumor.

Conclusion

Another phase 3 trial named XPORT-EC-042 has begun recruitment and has been scheduled to begin in June 2024. They are currently recruiting participants with recurrent or advanced endometrial cancer with aberrant p53 protein. The interventional drug will be Selinexor against a placebo.

References

Karyopharm Therapeutics Inc. (2023, December 5). Maintenance with selinexor/placebo after combination chemotherapy in participants with endometrial cancer [SIENDO]. ClinicalTrials.gov. https://www.clinicaltrials.gov/study/NCT03555422

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