A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Regorafenib Versus Placebo in Advanced/Metastatic, Treatment-Refractory Liposarcoma: Results from the SARC024 Study

Author:

Riedel Richard F.1,Ballman Karla V.2,Lu Yao2,Attia Steven3,Loggers Elizabeth T.4,Ganjoo Kristen N.5,Livingston Michael B.6,Chow Warren7,Wright Jennifer8,Ward John H.9,Rushing Daniel10,Okuno Scott H.11,Reed Damon R.12,Liebner David A.13,Keedy Vicki L.14,Mascarenhas Leo15,Davis Lara E.16,Ryan Christopher16,Reinke Denise K.17,Maki Robert G.18

Affiliation:

1. Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA

2. Weill Cornell Medicine, New York, New York, USA

3. Mayo Clinic, Jacksonville, Florida, USA

4. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

5. Stanford Cancer Institute, Stanford University, Stanford, California, USA

6. Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, USA

7. City of Hope Cancer Center, Duarte, California, USA

8. Eli Lilly and Company, Indianapolis, Indiana, USA

9. Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

10. Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA

11. Mayo Clinic, Rochester, Minnesota, USA

12. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

13. The Ohio State University, Columbus, Ohio, USA

14. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA

15. Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

16. Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA

17. Sarcoma Alliance for Research through Collaboration (SARC), Ann Arbor, Michigan, USA

18. Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

Abstract

Abstract Trial Information Click here to access other published clinical trials. 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 multitargeted kinase inhibitor with a kinase profile overlapping, but distinct from, pazopanib, an agent approved for recurrent and metastatic non-gastrointestinal stromal tumor (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 or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3 weeks 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 = .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 = .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.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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