In patients with wild-type TP53 advanced or recurrent endometrial cancer, the addition of maintenance therapy with selinexor following systemic therapy may prolong progression-free survival (PFS), according to research that will be presented during the July 2023 session of the American Society of Clinical Oncology (ASCO) Plenary Series.

According to the authors, approximately half of all patients with advanced or recurrent endometrial cancer have TP53 wild-type tumours and nearly all patients with advanced or recurrent endometrial cancer will experience recurrence within a short period of time. As there are currently no approved maintenance therapies for these patients, there is a critical need for effective maintenance therapies to delay cancer recurrence, which would also delay the initiation of second-line therapy.  

In this subgroup analysis of the phase 3 SIENDO study, 113 patients with TP53 wild-type advanced or recurrent endometrial cancer were randomly assigned to receive selinexor (n = 77) or placebo (n = 36) as maintenance therapy following response to prior systemic therapy. At a median duration of follow-up of 25.3 months, the prespecified exploratory subgroup of patients with TP53 wild-type advanced/recurrent endometrial cancer had a media progression-free survival of 27.4 months vs 5.2 months in the selinexor and placebo arms, respectively. According to the authors, the data also indicate that the TP53 wild type shows preliminary evidence of being a strong prognostic biomarker for the efficacy of selinexor.

The most common adverse events that led patients to stop taking selinexor included nausea, fatigue, asthenia (physical weakness and/or lack of energy), and vomiting. A majority of adverse events were of low grade and reversible with appropriate supportive therapy.

"This subset analysis of the phase 3 SIENDO trial examining TP53 wild-type tumours suggests use of selinexor following paclitaxel and carboplatin may be beneficial as maintenance therapy among patients at high risk for recurrence. Should these findings be confirmed in a definitive phase III study, it will give patients with TP53 wild-type tumours a new approach for preventing recurrence,” said Kathleen N. Moore, MD, MS, ASCO Expert in Gynaecologic Cancer.

“This is an exciting step forward in potential treatment options that will be studied further,” said Brian M. Slomovitz, MD, director of gynaecologic oncology at the Mount Sinai Medical Center in Miami Beach, Florida, and the lead author of the study. “With a weekly oral dose of selinexor, there is a possibility to remain progression-free for a much longer period than the current standard of care and substantially delay the initiation of second-line therapy.”

Source: ASCO