Selinexor Improves PFS, Time to Next Treatment in Metastatic, Advanced Dedifferentiated Liposarcoma

Second-line or later treatment with selinexor for metastatic, advanced dedifferentiated liposarcoma was associated with longer progression-survival (PFS) and time to next treatment compared to placebo, according to results from the phase 2/3 SEAL trial.

“Current treatment options of advanced dedifferentiated liposarcoma are limited in number and efficacy,” explained Mrinal Gounder, MD, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, and colleagues.

The multinational, double-blind, placebo-controlled SEAL trial aimed to assess the clinical benefit of selinexor in patients with dedifferentiated liposarcoma who progressed on approved agents. A total of 285 patients aged ≥12 were enrolled and randomized in a 2:1 ratio to selinexor (n = 188) or placebo (n = 97). Crossover was permitted on this trial.

The median PFS was 2.8 months with selinexor vs 2.1 months with placebo (hazard ratio [HR], 0.70; 95% confidence interval (CI), 0.52 to 0.95; one-sided P = .011). The median time to next treatment was 5.8 vs 3.2 months, respectively (HR 0.50; 95% CI, 0.37 to 0.66; P <.0001). Researchers reported no difference in overall survival with crossover.

The most common treatment-related adverse events were nausea, decreased appetite, and fatigue. Discontinuation due to treatment-emergent adverse events occurred in 9.1% of patients on selinexor and 4.1% of patients on placebo. There were 4 deaths reported in the selinexor arm and 3 in the placebo arm.

“In conclusion, to our knowledge, the SEAL trial was the first and largest study conducted exclusively on patients with heavily pretreated dedifferentiated liposarcoma,” wrote Dr Gounder and colleagues.

“Oral selinexor may represent a therapeutic option for patients with [dedifferentiated liposarcoma] who have exhausted treatments of known clinical benefit,” they concluded.

Source:                                        

Gounder M, Razak A, Somaiah N, et al. Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Oncol. Published online April 8, 2022. doi:10.1200/JCO.21.01829.