鶹ý

Maintenance Selinexor May Boost PFS in TP53 Wild-Type Advanced Endometrial Cancer

— Particularly strong PFS signal seen in patients that were mismatch repair proficient

MedpageToday

SEOUL, South Korea -- Maintenance therapy with selinexor (Xpovio) seemed to substantially extend progression-free survival (PFS) in patients with wild-type TP53 advanced or recurrent endometrial cancer, according to data from the SIENDO trial.

The updated, long-term data from the phase III study showed that, at a median follow-up of 25.3 months, median PFS was 27.4 months for 77 patients with TP53 wild-type tumors who received selinexor compared with 5.2 months among 36 patients who received placebo (HR 0.41, 95% CI 0.25-0.69, P=0.0002), reported Giovanni Scambia, MD, of the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome.

Moreover, a "strong PFS signal" was observed with selinexor maintenance therapy in the 47 patients with TP53 wild-type mismatch repair proficient (pMMR) disease -- a patient population with a high unmet need and for whom there is limited benefit with available therapies -- with PFS not reached versus 4.9 months in the 23 who received placebo (HR 0.32, 95% CI 0.16-0.64, P=0.0004), he said at the International Gynecologic Cancer Society annual meeting.

While not as strong, a PFS benefit was also demonstrated in 20 patients with TP53 wild-type mismatch repair deficient (dMMR) disease compared with the nine patients who received placebo (13.1 months versus 3.7 months, HR 0.45, 95% CI 0.16-1.27, P=0.0643).

"We know that TP53 wild-type status may represent a robust predictive biomarker for selinexor efficacy in endometrial cancer," Scambia said, adding that the results "highlight the potential opportunity to further personalize therapies" while providing a rationale for further evaluation of selinexor as maintenance therapy in the .

Scambia also reported preliminary survival results showing a positive overall survival (OS) trend with selinexor at a median follow-up of 28.9 months (HR 0.76, 95% CI 0.36-1.59, P=0.24) that was mostly driven by the TP53 wild-type pMMR group (HR 0.57, 95% CI 0.24-1.35, P=0.098).

Selinexor is an oral selective XP01 inhibitor that reactivates multiple tumor suppressive proteins, including wild-type p53, by preventing nuclear export. It currently has FDA approval as a treatment for and

The trial evaluated selinexor as maintenance treatment in patients with stage IV disease or a first relapse of endometrial cancer. After receiving 12 weeks of platinum-based chemotherapy and achieving either a complete or partial response, 263 patients were randomly assigned 2:1 to receive once-weekly oral selinexor or placebo.

In results reported at the 2022 Society of Gynecologic Oncology meeting, median PFS was 5.7 months with selinexor and 3.8 months with placebo at a median follow-up of 10.2 months. This was an absolute improvement of 1.9 months with selinexor that "was not clinically meaningful," Scambia said.

However, the PFS benefit was substantially greater among a subgroup of TP53 wild-type patients, with a median PFS for patients in the selinexor group of 13.7 months versus 3.7 months in the placebo group, translating into a 62% reduction in the risk of disease progression or death (HR 0.375, 95% CI 0.210-0.670, P=0.0003).

Thus, Scambia and colleagues focused this long-term follow-up on the group of 113 patients with wild-type TP53 tumors.

The most common adverse events (AEs) at any grade with selinexor were nausea, vomiting, and diarrhea, and the most common grade 3 or higher AEs were neutropenia, nausea, and thrombocytopenia.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was supported by Karyopharm.

Scambia disclosed multiple relationships with industry.

Primary Source

International Gynecologic Cancer Society

Sitarski A, et al "Long-term follow up of selinexor maintenance for patients with TP53wt advanced or recurrent endometrial cancer: A prespecified subgroup analysis from the phase 3 ENGOT-EN5/GOG-3055/SIENDO study" IGCS 2023; Abstract 1520.