Prospective double-blind, randomized phase III ENGOT-EN5/GOG-3055/SIENDO study of oral selinexor/placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer

Abstract

VP2-2022: Prospective double-blind, randomized phase III ENGOT-EN5/GOG-3055/SIENDO study of oral selinexor/placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer

Published: March 17, 2022
DOI: https://doi.org/10.1016/j.annonc.2022.02.223
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I.B. Vergote; A. Pérez Fidalgo; E. Hamilton; S. Shacham; M.R. Mirza; V. Makker
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Background

Patients (pts) with first-line metastatic or recurrent endometrial cancer (EC) are usually treated with paclitaxel and carboplatin but most have short-term disease control and a poor prognosis. Selinexor (SEL) inhibits XPO1 resulting in nuclear accumulation of p53, and has shown clinical activity in previously treated, advanced EC.

Methods

ENGOT-EN5/GOG-3055/ SIENDO (NCT03555422) is a prospective, multicenter, double-blind, placebo (PLB)-controlled, phase III study that evaluated SEL (80mg once weekly) vs PLB as maintenance therapy in pts with advanced or recurrent EC in partial or complete remission after taxane-platinum combination therapy. Primary endpoint compared progression-free survival (PFS) of SEL vs PLB, using a 2-sided stratified log-rank test. HR and the corresponding 2-sided 95% CI were estimated using stratified Cox proportional hazards model adjusting for stratification factors: primary stage IV disease vs recurrent disease at the start of combination chemotherapy and partial or complete response after chemotherapy.

Results

263 pts were randomized 2:1 to SEL (n=174) or PLB (n=89). Baseline characteristics were well balanced. Median follow up was 10.2 months (mo). The stratification adjusted analysis of PFS resulted in a HR of 0.705 (95% CI 0.499-0.996), p=0.048 (median 5.7 mo SEL vs 3.8 mo PLB). Subgroup analysis of EC pts with TP53wt showed a PFS of 13.7 mo with SEL and 3.7 mo with PLB (HR= 0.375, 95% CI 0.210-0.670, p=0.0006). Pts with MSS/pMMR disease had a PFS of 6.9 mo with SEL and 5.4 with PLB (HR= 0.593, 95% CI 0.388-0.905, p=0.014). Most common adverse events (AEs) (SEL/PLB) were nausea (83.6%/34.1%), vomiting (51.5%/17.0%), and constipation (37.4%/37.5%). Most AEs were low grade and reversible. Discontinuations due to AEs were 10.5% SEL and 1.1% PLB.

Conclusions

These results demonstrate that patients with advanced or recurrent EC administered once-weekly oral SEL have prolonged PFS compared to PLB with a manageable and tolerable safety profile. Pre-specified subgroup analyses identified wild-type TP53 and pMMR as important predictors of SEL efficacy.

Clinical trial identification

NCT03555422.