Maintenance Selinexor Showed Promise for Patients With Advanced or First-Line Recurrent TP53 Wild-Type Endometrial Cancer

According to subgroup analysis results from the phase 3 SIENDO study, maintenance selinexor demonstrated promising efficacy and safety among patients with advanced or first-line recurrent TP53 wild-type (wt) endometrial cancer. 

“Identification of a maintenance therapy after response to chemotherapy in advanced or first-line recurrent [endometrial cancer] is an important treatment option,” stated Vicky Makker, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors. Despite discouraging primary results in the intention-to-treat population, “an exploratory analysis of a prespecified subgroup of patients with TP53wt [endometrial cancer] showed a promising efficacy signal.” This prespecified subgroup analysis reports the long-term follow-up of efficacy and safety data from the cohort of patients with TP53wt disease.

In the TP53wt subgroup of this double-blind trial, there were 113 patients with TP53wt advanced or first-line recurrent endometrial cancer who received ≥ 12 weeks of taxane-platinum-based chemotherapy and achieved partial or complete remission. Patients were randomized on a 2-to-1 basis to receive either 80 mg of once weekly selinexor (n = 77) or placebo (n = 36). Of the 99 patients with known MMR status, 70 were proficient mismatch repair (pMMR) and 29 were deficient mismatch repair (dMMR). The exploratory end points for this analysis was investigator-assessed progression-free survival (PFS) in the prespecified subgroup of patients with TP53wt disease, and across further subgroups within that population, including MMR status, response after most recent chemotherapy, complete or partial response, and others.

At a median follow-up of 36.8 months, median PFS within the TP53wt subgroup was 28.4 months in the selinexor arm and 5.2 months in the placebo arm (hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.27 to 0.73; P = .0005). Further, with 38.5 months of follow-up, patients with pMMR status had a median PFS of 39.5 months with selinexor vs 4.9 months with placebo (HR 0.36; 95%CI 0.19 to 0.71; P = .0011). With 32.8 months of follow-up, patients with dMMR status had a median PFS of 13.1 months with selinexor and 3.7 months with placebo (HR 0.49; 95% CI, 0.18 to 1.34; P = .0825). There was a benefit to PFS with selinexor across all subgroups and irrespective of whether the patient achieved a partial or complete response. Study authors also noted, “The clinical benefit was potentially stronger in the TP53wt/pMMR subgroup compared with placebo.”

The most common grade ≥3 treatment-emergent adverse events included neutropenia, nausea, and thrombocytopenia. In the selinexor arm, there were 13 patients who experienced a treatment-emergent adverse event which led to discontinuation (placebo, n = 0) and 60 with a treatment-emergent adverse event which led to dose modification (placebo, n = 10).

“The positive results of this subgroup analysis highlight the potential opportunity to further personalize therapies and provide a strong rationale to further evaluate selinexor as maintenance therapy in patients with TP53wt advanced or recurrent [endometrial cancer],” concluded Dr Makker et al. 

Source: 

Makker V, Perez-Fidalgo JA, Valbrega G, et al. Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study. Gynecol Oncol. Published online: June 3, 2024. doi: 10.1016/j.ygyno.2024.05.016