Post-hoc analysis evaluating selinexor maintenance therapy in patients with <i>TP53</i> wt endometrial cancer: Progression-free survival by clinical factors in the ENGOT-EN5/GOG-3055/SIENDO study.

Abstract

5608 Background: At primary analysis of the phase 3 study of selinexor (SEL) maintenance treatment in patients (pts) with advanced/recurrent endometrial cancer (EC), improvement in median progression-free survival (PFS) for the intent-to-treat population was not clinically meaningful. However, a promising efficacy signal was seen in a pre-specified exploratory analysis of TP53 wt EC. We present further exploratory PFS analyses of long-term follow-up data in TP53 wt EC. Methods: ENGOT-EN5/GOG-3055/SIENDO (NCT03555422) was a double-blind randomized (2:1) study evaluating SEL vs placebo as maintenance treatment in pts with advanced/recurrent EC following response to prior systemic therapy. Post-hoc exploratory subgroup analyses include response to prior systemic chemotherapy, disease at time of prior systemic therapy, Eastern Cooperative Oncology Group (ECOG) performance status, histopathological subtype at initial diagnosis, and duration of last systemic therapy. Additional subgroups will be reported at the time of presentation. Results: Of 263 pts in the study, 113 (43.0%) had TP53 wt EC (SEL, n = 77; placebo, n = 36). At data cut-off (April 1, 2024), PFS subgroup analyses generally showed benefit for SEL compared with placebo in the TP53 wt subgroup regardless of clinical factor (table). Adverse events (AEs) were generally manageable and reversible. The most common AEs (overall/Grade ≥3) with SEL were nausea (89.5%/13.2%), vomiting (60.5%/2.6%), and diarrhea (44.7%/3.9%). Dual anti-emetics were not mandated. No meaningful differences in AEs were observed across subgroups. 17.1% of pts discontinued SEL due to AEs; 1 death occurred in the placebo group. Conclusions: A strong PFS signal was observed in the TP53 wt subgroup across a range of key clinical factors at long-term follow-up. Efficacy and safety of SEL maintenance therapy were generally comparable across subgroups. A phase 3 trial is ongoing to further investigate SEL as maintenance therapy in pts with advanced/recurrent TP53 wt EC (ENGOT-EN20/GOG-3083/Xport-EC-042, NCT05611931). Clinical trial information: NCT03555422 . Placebo, e/n(N = 36) SEL, e/n(N = 77) PFS, HR vs placebo (95% CI) Response to prior therapy: PR 18/20 31/46 0.50 (0.27, 0.92) CR 9/16 7/31 0.24 (0.09, 0.67) Disease at time of prior therapy: Primary Advanced 12/17 18/34 0.58 (0.28, 1.21) Recurrent 15/18 18/41 0.29 (0.14, 0.61) ECOG: 0 16/22 20/43 0.24 (0.11, 0.53) 1 or 2 11/14 18/34 0.50 (0.20, 1.26) Histopathological subtype: Endometrioid 22/29 33/65 0.45 (0.25, 0.79) Non-endometroid 5/7 5/12 0.31 (0.07, 1.34) Duration of last systemic therapy: 12 to &lt;24 weeks 20/27 28/60 0.45 (0.25, 0.81) ≥24 weeks 7/9 10/17 0.66 (0.25, 1.74) CI, confidence interval; CR, complete response; ECOG, Eastern Cooperative Oncology Group; e/n, patients with events/(patients with events + patients censored); HR, hazard ratio; PR, partial response.