Phase II Study of Regorafenib in Metastatic Osteosarcoma


Key Points

  • Regorafenib prolonged progression-free survival vs placebo.
  • Median progression-free survival was 3.6 vs 1.7 months.

As reported in the Journal of Clinical Oncology by Davis et al, outcomes in the osteosarcoma cohort of the phase II SARC024 trial indicated a progression-free survival benefit with regorafenib vs placebo in previously treated metastatic osteosarcoma.

Study Details

The randomized double-blind trial evaluated regorafenib in four sarcoma subtypes; the current report is of outcomes in the osteosarcoma cohort. 

In the trial, 42 patients with metastatic osteosarcoma with at least 1 prior line of therapy (average prior therapy regimens = 2.3) from 12 centers in the United States were randomly assigned between September 2014 and May 2018. Patients received either regorafenib 160 mg once daily on days 1 to 21 in 28-day cycles (n = 22) or placebo (n = 20), with treatment continuing until progression. Crossover to regorafenib was allowed at time of progression. 

The primary endpoint was progression-free survival. 

Progression-Free Survival

Study enrollment was stopped early, after review by a data safety monitoring committee. 

Median follow-up among surviving patients was 7.4 months. Median progression-free survival was 3.6 months in the regorafenib group vs 1.7 months in the placebo group (hazard ratio [HR] = 0.42, P= .017). Progression-free survival was 79.0% vs 25.0% at 8 weeks and 44.4% vs 10.0% at 16 weeks. 

Ten patients in the placebo group crossed over to regorafenib treatment at time of progression. Median overall survival was 11.1 months vs 13.4 months (HR = 1.26, P = .62), with assessment of survival not taking into account the high crossover rate from placebo to regorafenib.

Adverse Events

The most common treatment-related adverse events of any grade in the regorafenib group were hand-foot skin reaction (36% vs 0% in placebo group) and hypertension (32% vs 15%). Grade ≥ 3 treatment-related adverse events occurred in 64% of the regorafenib group vs 45% of the placebo group, with the most common in the regorafenib group being hypertension (14%). One grade 4 event occurred in the regorafenib group (colonic perforation).  

The investigators concluded, “The study met its primary endpoint, 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.”

Lara E. Davis, MD, of Oregon Health & Sciences University, Portland, is the corresponding author for the Journal of Clinical Oncology article. 

Disclosure: The study was supported in part by Bayer HealthCare Pharmaceuticals. For full disclosures of the study authors, visit

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