Selinexor Showed Longer PFS Vs Placebo in Patients with Advanced, Metastatic DD-LPS

Results of the SEAL study revealed a 30% progression-free survival improvement in patients with advanced, metastatic dedifferentiated liposarcoma who underwent selinexor therapy as well as other efficacy and safety benefits.

Patients with advanced, metastatic dedifferentiated liposarcoma (DD-LPS) who received selinexor (Xpovio) experienced favorable progression-free survival (PFS) and time-to-next treatment compared with patients who received placebo.1

Patients treated with selinexor reported a 30% improvement in median PFS over placebo with the median PFS of selinexor at 2.8 months vs 2.1 months with placebo (HR 0.70; 95% CI, 0.52-0.95; one-sided P = .01; two-sided P = .02).PFS results continued to favor selinexor at 12 weeks or more with a PFS of 46.8% (95% CI, 39.6%-55.1%) among 88 patients vs a PFS of 34% (95% CI, 29.1%-50.7%) among 33 patients who received placebo (one-sided P = .02; two-sided P = .04). The 6-month PFS rate for selinexor and placebo were 23.9% (95% CI, 17.7%-32.4%) vs 13.9% (95% CI, 29.1%-50.7%), respectively, and the 12-month PFS rate was 8.4% (95% CI, 4.3%-16.2%) vs 2.0% (95% CI, 0.3%-13.4%), respectively. Of the 135 (71.8%) PFS events in the selinexor arm and 74 (76.3%) PFS events in the placebo arm, there were 10 (5.3%) deaths with selinexor and 5 (5.2%) with placebo.

The phase 2/3, multicenter, randomized, double-blind SEAL study (NCT02606461) enrolled and randomized 285 patients with DD-LPS 2:1 to receive selinexor (n = 188) or placebo (n = 97). Investigators administered 60 mg of selinexor or matching placebo twice a week in 6-week cycles. Random assignment was stratified on the basis of prior eribulin use, prior trabectedin use, and the number of prior systemic therapies, excluding eribulin and trabectedin. Eligible patients must have been 12 years or older, had histologically confirmed DD-LPS with measurable disease per RECIST v1.1 as assessed by an independent review committee, had shown radiologic evidence of disease progression, had received between 2 and 5 prior systemic therapies, an ECOG performance status of 1 or less, creatinine clearance less than 30 mL/min, and adequate laboratory hematopoietic and hepatic function. The study excluded patients with othersubtypes of liposarcoma or with known central nervous system metastases.

The primary end point was PFS, defined as the time from date of random assignment until the first date of progression confirmed by RECIST v1.1 or death. The secondary end points were overall survival (OS), time to progression on study treatment, overall response rate (ORR), duration of response (DOR), time to next treatment, and health-related quality of life.

ORR occurred in 5 patients (2.7%) treated with selinexor, whereas no responses were observed with placebo. The median DOR was 7.4 months with selinexor. The median time to next treatment was 5.8 months with selinexor vs 3.2 months with placebo (HR 0.49 [95% CI, 0.37-0.66], one-sided P < .0001; two-sided P = .0002). Investigators found no significant difference in OS for patients treated with selinexor, at 10.0 months, and placebo, at 12.9 months, with a median follow up of 14.6 months (HR, 1.02; 95% CI, 0.73-1.42, one-sided P = .54; two-sided P = 1.08).

The median age for patients in both treatment arms was 65 years. The majority of patients were male with both arms consisting of at least 60% male. Most patients reported an ECOG performance score of 1 with 117 patients (62.2%) in the selinexor arm and 56 patients (57.7%) in the placebo arm.

Treatment emergent adverse events (TEAEs) caused treatment discontinuation in 17 patients (9.1%) in the selinexor arm and in 4 patients (4.1%) in the placebo arm. More patients in the selinexor arm required dose reduction and dose interruption because of AEs (35.8% and 63.1%, respectively) compared with the placebo arm (3.1% and 16.5%, respectively).The most commonly reported TEAEs in both the selinexor and placebo groups were nausea (80.7% vs 39.2%), decreased appetite (60.4% vs 22.7%), fatigue (51.3% vs 32.0%), and weight loss (42.2% vs 9.3%). The most common grade 3 or 4 AEs for the selinexor and placebo arms were anemia (18.7% vs 8.2%), hyponatremia (10.7% vs 0%), asthenia (10.2% vs 0%), and thrombocytopenia (10.2% vs 0%). Serious TEAEs affected 71 patients (38%) in the selinexor arm vs 18 patients (18.6%) in the placebo arm. TEAEs leading to death occurred in 2.1% of patients receiving selinexor and in 3.1% of patients receiving placebo.

In conclusion, the results of the SEAL study revealed a 30% PFS improvement in patients who underwent selinexor therapy including clinical benefits seen in 3-, 6- and 12-month PFS rates.Most AEs were more commonly low grade and reversible. Proactive, supportive care can mitigate these AEs.

REFERENCE

Gounder MM, Razak AA, Somaiah N, et al. Selinexor in advanced, metastatic dedifferentiated liposarcoma: a multinational, randomized, double-blind, placebo-controlled trial. Published online April 8, 2022. J Clin Oncol. 2022;JCO2101829. doi:10.1200/JCO.21.01829