Abstract

LESSONS LEARNED: The results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist.BACKGROUND: Regorafenib is a multi-targeted kinase inhibitor with a kinase profile overlapping, but distinct from pazopanib, an agent approved for recurrent/metastatic non-gastrointestinal tumors (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients.METHODS: Patients with advanced/metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1.RESULTS: Forty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI]: 0.92-3.67) months for regorafenib versus 2.07 (95% CI: 1.64-3.44) months for placebo; stratified hazard ratio [HR] 0.85 (95% CI: 0.46, 1.58), p value = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI: 4.16-23.48) months for regorafenib and 4.89 (95% CI: 3.02-9.77) months for placebo, stratified HR 0.66 (95% CI: 0.31-1.40), p value = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib.CONCLUSION: Regorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.

View details for DOI 10.1634/theoncologist.2020-0679

View details for PubMedID 32701199