Regorafenib in Previously Treated Metastatic Osteosarcoma


Key Points

  • Regorafenib was associated with a higher rate of absence of progression at 8 weeks vs placebo.
  • Absence of progression was found in 65% vs 0% of patients.

In a phase II trial reported in The Lancet Oncology, Duffaud et al found evidence of activity of regorafenib (Stivarga) in a cohort of adult patients with previously treated metastatic osteosarcoma.

This noncomparative, double-blind trial involves 4 cohorts of patients, consisting of those with osteosarcoma, Ewing sarcoma, chondrosarcoma, or chordoma. The current report provides findings in the osteosarcoma cohort. 

Methodology and Outcomes

In the cohort, 38 evaluable adult patients from 13 French sites whose disease had progressed after treatment with 1 to 2 previous lines of chemotherapy for metastatic disease were randomly assigned 2:1 between October 2014 and April 2017 to receive oral regorafenib at 160 mg/d (n = 26) or placebo (n =12) for 21 days in 28-day cycles, with patients in both groups also receiving best supportive care.

The primary endpoint was the proportion of patients without disease progression on Response Evalulation Criteria in Solid Tumors, version 1.1, at 8 weeks. Patients in the placebo group were permitted to receive regorafenib after disease progression. The results represent the final analysis of the osteosarcoma cohort; other cohorts are ongoing.

Absence of progression at 8 weeks was found in 17 (65%) of 26 patients in the regorafenib group vs 0 (0%) of 12 patients in the placebo group. Two partial responses were observed in the regorafenib group, with response durations of 6.2 and 12.9 months; no responses were observed in the placebo group. Median progression-free survival was 16.4 weeks vs 4.1 weeks.

Adverse Events

Among the 43 patients who received at least 1 dose of study drug, treatment-related serious adverse events occurred in 7 (24%) of 29 in the regorafenib group vs 0 (0%) of 14 in the placebo group. The most common grade ≥ 3 treatment-related adverse events during the double-blind treatment period included hypertension (24% of regorafenib group vs 0% of placebo group), hand-foot skin reaction (10% vs 0%), fatigue (10% vs 3%), hypophosphatemia (10% vs 0%), and chest pain (10% vs 0%). No treatment-related deaths were observed.

The investigators concluded, “Regorafenib demonstrated clinically meaningful antitumour activity in adult patients with recurrent, progressive, metastatic osteosarcoma after failure of conventional chemotherapy, with a positive effect on delaying disease progression. Regorafenib should be further evaluated in the setting of advanced disease as well as potentially earlier in the disease course for patients at high risk of relapse. Regorafenib might have an important therapeutic role as an agent complementary to standard cytotoxic chemotherapy in the therapeutic armamentarium against osteosarcoma.”

Florence Duffaud, MD, Hôpital La Timone, Service d’Oncologie Médicale, Marseille, is the corresponding author of The Lancet Oncology article.

Disclosure: The study was funded by Bayer HealthCare. The study authors’ full disclosures can be found at

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