Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind,...

Area of Science:

• Oncology
• Medical Research
• Clinical Trials

Background:

• Selinexor has shown antitumor activity in preclinical models and Phase I studies for dedifferentiated liposarcoma (DD-LPS).
• Previous treatments for advanced DD-LPS have limited efficacy, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate the clinical benefit of selinexor in patients with previously treated advanced DD-LPS.
• To assess the efficacy and safety of selinexor compared to placebo in refractory DD-LPS.

Main Methods:

• The SEAL study was a Phase II-III, multicenter, randomized, double-blind, placebo-controlled trial.
• Patients with advanced DD-LPS received selinexor (60 mg) or placebo twice weekly in 6-week cycles.
• The primary endpoint was progression-free survival (PFS); safety analysis included all patients receiving at least one dose.

Main Results:

• Selinexor significantly improved PFS (HR 0.70; P=.011) and time to next treatment (HR 0.50; P<.0001) compared to placebo.
• Common adverse events with selinexor included nausea, decreased appetite, and fatigue, manageable with supportive care and dose reductions.
• Exploratory analysis indicated that absence of CALB1 expression was associated with longer PFS in patients treated with selinexor.

Conclusions:

• Selinexor offers a clinical benefit for patients with advanced, refractory DD-LPS, improving PFS and time to next treatment.
• Supportive care and dose adjustments can effectively manage selinexor's side effects.
• CALB1 expression may serve as a predictive biomarker for selinexor efficacy in DD-LPS, warranting prospective validation.