Cabozantinib for Advanced Ewing Sarcoma or Osteosarcoma

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In the French phase II CABONE trial reported in The Lancet Oncology, Italiano et al found that the MET and VEGFR2 inhibitor cabozantinib was active in patients with advanced Ewing sarcoma or osteosarcoma.

Study Details

In the multicenter trial, 81 evaluable patients aged ≥ 12 years with progressive Ewing sarcoma (n = 39) or osteosarcoma (n = 42) received cabozantinib at 60 mg (adults) and 40 mg/m2 (those aged < 16 years) once daily in 28-day cycles until disease progression or unacceptable toxicity.

The primary endpoint for Ewing sarcoma was best objective response within 6 months of the start of treatment; for osteosarcoma, the dual primary endpoint was 6-month objective response and 6-month nonprogression. The majority of patients had received one or more prior treatment for advanced disease.


Median follow-up was 31.3 months in the Ewing sarcoma group and 31.1 months in the osteosarcoma group. Among patients with Ewing sarcoma, 10 (26%) had an objective response (all partial responses) by 6 months, and an additional 19 (49%) had stable disease. Median progression-free survival was 4.4 months, and median overall survival was 10.2 months.

Among patients with osteosarcoma, 5 (12%) had an objective response (all partial responses) at 6 months, and 14 (33%) had 6-month nonprogression; stable disease was observed in 26 patients (62%). Median progression-free survival was 6.7 months, and median overall survival was 10.6 months.


  • Objective response was observed in 26% of patients with Ewing sarcoma.
  • Among patients with osteosarcoma, objective response was observed in 12%, and nonprogression at 6 months was observed in 33%.

Adverse Events

Among 90 patients (45 in each group) assessable for safety, the most common grade 3 or 4 adverse events were hypophosphatemia (11% of the Ewing sarcoma group and 7% of the osteosarcoma group), aspartate aminotransferase increase (4% and 7%), palmar-plantar syndrome (7% and 4%), pneumothorax (2% and 9%), and neutropenia (4% and 9%). Serious adverse events were reported in 68% of patients. No treatment-related deaths were observed.

The investigators concluded, “Cabozantinib has antitumor activity in patients with advanced Ewing sarcoma and osteosarcoma and was generally well tolerated. Cabozantinib could represent a new therapeutic option in this setting and deserves further investigation.”

Antoine Italiano, MD, of the Early Phase Trials and Sarcoma Unit, Institut Bergonie, Bordeaux, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the Institut Bergonié, French National Cancer Institute, and Association pour la Recherche contre le Cancer. For full disclosures of the study authors, visit

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