Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma

Davis, L. E., Bolejack, V., Ryan, C. W., Ganjoo, K. N., Loggers, E. T., Chawla, S., Agulnik, M., Livingston, M. B., Reed, D., Keedy, V., Rushing, D., Okuno, S., Reinke, D. K., Riedel, R. F., Attia, S., Mascarenhas, L., Maki, R. G. (June 2019) Randomized Double-Blind Phase II Study of Regorafenib in Patients With Metastatic Osteosarcoma. J Clin Oncol, 37 (16). pp. 1424-1431. ISSN 0732-183x

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URL: https://www.ncbi.nlm.nih.gov/pubmed/31013172
DOI: 10.1200/jco.18.02374


PURPOSE: SARC024 is a phase II clinical trial of the multikinase inhibitor regorafenib in specific sarcoma subtypes, including advanced osteosarcoma. We hypothesized that regorafenib would improve progression-free survival (PFS) in patients with sarcoma and report the results of the osteosarcoma cohort. PATIENTS AND METHODS: This trial enrolled patients with progressive metastatic osteosarcoma with measurable disease by RECIST who had received at least one prior line of therapy. Patients were randomly assigned at a ratio of one to one to regorafenib or placebo. Crossover was allowed at time of disease progression. PFS was the primary end point of the study, which was powered to detect a difference of at least 3 months in median PFS. RESULTS: Forty-two patients from 12 centers were enrolled between September 2014 and May 2018. Median age was 37 years (range, 18 to 76 years). Patients had received an average of 2.3 prior therapy regimens. Ten patients receiving placebo crossed over to active drug at time of progression. Study enrollment was stopped early, after a data safety monitoring committee review. Median PFS was significantly improved with regorafenib versus placebo: 3.6 months (95% CI, 2.0 to 7.6 months) versus 1.7 months (95% CI, 1.2 to 1.8 months), respectively (hazard ratio, 0.42; 95% CI, 0.21 to 0.85; P = .017). In the context of the crossover design, there was no statistically significant difference in overall survival. Fourteen (64%) of 22 patients initially randomly assigned to regorafenib experienced grade 3 to 4 events attributed to treatment, including one grade 4 colonic perforation. CONCLUSION: The study met its primary end point, demonstrating activity of regorafenib in patients with progressive metastatic osteosarcoma. No new safety signals were observed. Regorafenib should be considered a treatment option for patients with relapsed metastatic osteosarcoma.

Item Type: Paper
Subjects: diseases & disorders > cancer > drugs and therapies > chemotherapy
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matthew Dunn
Date: 1 June 2019
Date Deposited: 22 May 2019 16:52
Last Modified: 29 Jun 2021 19:12
PMCID: PMC7799443
Related URLs:
URI: https://repository.cshl.edu/id/eprint/37829

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