SIENDO/ENGOT-EN5/GOG-3055: A randomized phase 3 trial of maintenance selinexor versus placebo after combination platinum-based chemotherapy in advanced or recurrent endometrial cancer.

Abstract

TPS5610 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Options for advanced or recurrent EC following platinum-based therapy and/or radiotherapy are limited and prognosis remains poor. Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) which forces nuclear retention and activation of tumor suppressor proteins. Selinexor in combination with low dose dexamethasone is approved for relapsed/refractory multiple myeloma. In addition, selinexor monotherapy has demonstrated broad activity in other hematologic malignancies and solid tumors. In a phase 2 study, 50 mg/m2 (̃80 mg) selinexor administered twice weekly demonstrated a disease control rate ( SD ≥ 12 weeks or a PR) of 35% with 2 confirmed partial responses among 23 heavily pretreated EC patients); similar results were observed in 60 pts with platinum resistant or refractory ovarian cancer (median 5 prior regimens, ORR 8%, DCR 30%) (Vergote I et al. Gynecol Oncol 2020). In the absence of approved maintenance therapies, we conducted this study to evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent EC following platinum-based chemotherapy. Methods: This is a multicenter, double-blind, placebo-controlled, randomized phase 3 study in patients in partial (PR) or complete remission (CR) after completing at least 12 weeks of taxane-platinum combination therapy for primary Stage IV disease and recurrent disease (i.e., relapse after primary therapy for early stage disease including surgery and/or adjuvant therapy). A total of 248 patients will be enrolled at 80 sites in Europe, North America, and Israel. Patients will be randomized in a 2:1 ratio to either maintenance therapy with 80 mg oral selinexor once weekly or placebo. Stratification factors include primary Stage IV versus first recurrence at the time of taxane-platinum therapy and disease status after chemotherapy (PR vs CR). Treatment will continue until disease progression. The primary endpoint is progression free survival (PFS) per RECIST v1.1. Secondary endpoints include disease-specific survival, overall survival, time to first subsequent therapy, time to second subsequent therapy, PFS on subsequent therapy and safety and tolerability. The study is currently open and enrolling patients. Clinical trial information: NCT03555422.

What Has Changed in the Management of Uterine Serous Carcinomas? Two Decades of Experience

“…Several molecular signaling pathways, including the PI3K/AKT/mTOR pathway and mechanism of Poly (ADP-Ribose) Polymerase-1 (PARP-1), are under investigation for the development of novel transformative therapies that have the potential to impact patients’ survival [ 57 , 58 ]. Ongoing randomized clinical trials that enroll patients with USC evaluate in the first-line setting, the efficacy and safety of (1) Antiangiogenetic treatment plus chemotherapy [ 59 ], (2) PARPi and anti-PD-1/PD-L1 combinations as maintenance treatment after first-line chemotherapy [ 60 ], and (3) the Selective inhibitor of Nuclear Export (SINE), Selinexor as maintenance treatment post platinum-based chemotherapy [ 61 ].…”

Major clinical research advances in gynecologic cancer in 2023: a tumultuous year for endometrial cancer

“…Selinexor is currently undergoing trials in endometrial cancer with p53 wild type. EC-042 (XPORT-EC-042; NCT05611931) is a global, phase 3, randomized, double-blind study evaluating Selinexor (60 mg QW) as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer [ 39 ].…”