In the phase II/III SEAL trial reported in the the Journal of Clinical Oncology, Gounder et al found that selinexor significantly improved progression-free survival and time to subsequent treatment in previously treated advanced dedifferentiated liposarcoma, with the greatest benefit observed in patients with tumors exhibiting no detectable CALB1 expression.
In the double-blind trial, 285 patients aged ≥ 12 years with advanced unresectable disease from sites in 10 countries who had received two to five prior lines of therapy were randomly assigned 2:1 to receive selinexor at 60 mg (n = 188) or placebo (n = 97) twice weekly in 6-week cycles. The majority of patients had metastatic disease and had received doxorubicin, gemcitabine, eribulin, or trabectedin.
Crossover was permitted in the placebo group upon disease progression. The primary endpoint was progression-free survival.
The selinexor group exhibited significantly prolonged progression-free survival (hazard ratio (HR) = 0.70, 95% confidence interval [CI] = 0.52–0.95, P = .011), with median durations of 2.8 vs 2.1 months. The selinexor group also exhibited significantly prolonged time to next treatment (HR = 0.50, 95% CI = 0.37–0.66, P < .0001, with median durations of 5.8 vs 3.2 months.
In an exploratory analysis among 30 patients with tumors that had no detectable CALB1 expression (16 in the selinexor group, 14 in the placebo group), median progression-free survival was 6.9 vs 2.2 months (HR = 0.19, 95% CI = 0.07–0.56, P = .001). In the selinexor group, median progression-free survival was 6.9 vs 1.7 months (HR = 0.45, 95% CI = 0.21–0.95, P = .03) among patients without vs with tumors with CALB1 expression. No association of progression-free survival with CALB1 expression was observed in the placebo group (P = .44).
The most common adverse events of any grade in the selinexor group were nausea (80.7% vs 39.2% in placebo group), 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 adverse events were anemia (18.7% vs 8.2%), hyponatremia (10.7% vs 0%), asthenia (10.2% vs 0%), and thrombocytopenia (10.2% vs 0%). Serious adverse events occurred in 38.0% vs 18.6% of patients, most commonly gastrointestinal events in both groups (11.8% vs 6.2%). Fatal adverse events occurred in four patients (2.1%) vs three patients (3.1%).
The investigators concluded: “Patients with advanced, refractory [dedifferentiated liposarcoma] showed improved [progression-free survival] and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in [dedifferentiated liposarcoma] is warranted.”
Mrinal M. Gounder, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Karyopharm Therapeutics, Inc. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.