SARC024: Regorafenib in Metastatic Osteosarcoma


Key Points

  • Median progression-free survival was 3.6 vs 1.7 months.
  • Ten patients in the placebo group crossed over to regorafenib at disease progression.

In the phase II SARC024 trial in sarcoma subtypes reported in the Journal of Clinical Oncology, Davis and colleagues found that regorafenib improved progression-free survival vs placebo in the cohort of patients with metastatic osteosarcoma.

The double-blind study included 42 patients from 12 U.S. centers with progressive metastatic osteosarcoma and measurable disease who had received at least one prior line of therapy. Patients were randomly assigned between September 2014 and May 2018 to receive oral regorafenib at an initial dose of 160 mg on days 1 to 21 of 28-day cycles (n = 22) or placebo (n = 20).

Patients received study treatment until disease progression, elapsing of more than 28 days since last dose, or patient- or physician-initiated discontinuation. Patients in the placebo group were permitted to cross over to receive regorafenib at disease progression.

The primary endpoint was progression-free survival. Study enrollment was stopped early on the basis of a data safety monitoring committee review.

Progression-Free Survival

Median progression-free survival was 3.6 months (95% confidence interval [CI] = 2.0–7.6 months) in the regorafenib group vs 1.7 months (95% CI = 1.2–1.8 months) in the placebo group (hazard ratio [HR] = 0.42, P = .017). Objective response was observed in three patients treated with regorafenib and no patients treated with placebo.

Ten patients in the placebo group crossed over to regorafenib at disease progression. No significant difference in overall survival was observed between the initial randomized groups (median = 11.1 vs 13.4 months, HR = 1.26; P = .62). Median overall survival was 11 months from the start of crossover treatment for the 10 patients who crossed over to regorafenib.

Adverse Events

Treatment-related grade 3 or 4 adverse events occurred in 64% of the regorafenib group, with the most common being hypertension (14%), maculopapular rash (9%), thrombocytopenia (9%), hypophosphatemia (9%), and extremity pain (9%). One patient had grade 4 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 by Bayer HealthCare Pharmaceuticals. For full disclosures of the study authors, visit

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