Cabozantinib in the treatment of advanced Ewing sarcoma and osteosarcoma

The Lancet Oncology reported on the French phase II CABONE clinical trial, in which Italiano and colleagues found activity in patients with advanced Ewing sarcoma or osteosarcoma with cabozantinib, an inhibitor of MET and VEGFR2.

- Related topic: What is Ewing sarcoma? Symptoms and treatment (in detail)

Note: Cabozantinib had previously been approved in 2016 for advanced renal cell cancer (see); in 2017 for previously untreated advanced renal cell cancer (see); and in 2019 for previously treated advanced hepatocellular cancer (see) by the FDA. In Turkey, it is licensed only for use in kidney cancer.

Details of the CABONE study

In this multicenter study, 39 patients with Ewing sarcoma and 42 patients with osteosarcoma whose disease had progressed on treatment received cabozantinib in 28-day cycles, 1 dose of 60 mg per day, until disease progression or unacceptable side effects developed.

The primary endpoint for Ewing sarcoma, assessed within 6 months after treatment began, was the best objective response; for osteosarcoma, dual primary endpoints were defined: objective response at 6 months and progression-free survival at 6 months. Most patients had already received at least 1 line of treatment for their advanced cancer.

Results

• Median follow-up was 31.3 months in the Ewing sarcoma group and 31.1 months in the osteosarcoma group.
• An objective response was observed in 10 patients with Ewing sarcoma (26%) by 6 months; all of these were partial responses. In addition, 19 patients (49%) had stable disease.
• Median progression-free survival was 4.4 months and median overall survival was 10.2 months.

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• An objective response was observed in 5 patients with osteosarcoma (12%) at 6 months (all partial responses).
• A total of 14 patients (33%) had no progression within 6 months, and stable disease was observed in 26 patients (62%).
• Median progression-free survival was 6.7 months and median overall survival was 10.6 months.

Notable findings

An objective response was observed in 26% of patients with Ewing sarcoma. Among patients with osteosarcoma, 12% had an objective response and 33% had no progression at 6 months.

Side effects

Among the 90 patients evaluable for safety (45 in each group), the most common severe (grade 3 and 4) side effects were hypophosphatemia (11% in the Ewing sarcoma group and 7% in the osteosarcoma group), increased aspartate aminotransferase (4% and 7%), hand-foot syndrome (7% and 4%), pneumothorax (2% and 9%) and neutropenia (4% and 9%). Severe side effects were reported in 68% of patients. No treatment-related deaths were observed.

In conclusion, cabozantinib is effective and was generally well tolerated in patients with advanced Ewing sarcoma and osteosarcoma, for whom treatment options are very limited. Cabozantinib may gain approval as a new treatment option for these patients and will be tested in a phase-III study.