The discovery sheds new light on its potential role in the management of a disease that affects roughly half of all advanced or recurrent endometrial cancer patients.
Maintenance therapy with selinexor, an oral exportin 1 (XPO1) inhibitor, has been found to substantially extend progression-free survival (PFS) in patients with wild-type TP53 advanced or recurrent endometrial cancer. A subset analysis of the phase 3 SIENDO trial, presented at the July 2023 session of ASCO, shows a dramatic improvement in median PFS in a specific group of patients.
Key Points:
- SIENDO trial evaluated selinexor vs. placebo in 263 patients with advanced or recurrent endometrial cancer in remission.
- Median PFS was 27.4 months with selinexor vs. 5.2 months with placebo in wild-type TP53 patients, at a median follow-up of 25.3 months.
- Most common adverse events include nausea, vomiting, diarrhea; grade 3 or higher included neutropenia, nausea, thrombocytopenia.
- Selinexor has FDA approval for relapsed or refractory multiple myeloma and diffuse large B-cell lymphoma but is investigational for endometrial cancer.
Additional Points:
- The new data is described as “unprecedented” and provides a plausible biological hypothesis for this subset benefit.
- A new phase 3 trial (XPORT-EC-042) is underway, focusing on p53 wild-type advanced or recurrent endometrial cancer with 220 participants targeted.
Conclusion:
- The significant PFS benefit with selinexor opens a promising avenue in treating wild-type TP53 endometrial cancer, with ongoing research to confirm and explore these remarkable findings.
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