Cabozantinib Shows Promising Activity in Osteosarcoma and Ewing Sarcoma

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Cabozantinib demonstrated efficacy in osteosarcoma and Ewing sarcoma in 2 single-arm, phase 2 trials, with objective response rates of 45% and 58%, respectively.
Cabozantinib demonstrated efficacy in osteosarcoma and Ewing sarcoma in 2 single-arm, phase 2 trials, with objective response rates of 45% and 58%, respectively.
The following article features coverage from the European Society for Medical Oncology (ESMO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

Cabozantinib demonstrated efficacy in advanced osteosarcoma and Ewing sarcoma, according to the results of 2 phase 2 trials presented at the ESMO 2018 Congress in Munich, Germany.1

The outcomes for patients with relapsed and unresectable osteosarcoma and Ewing sarcoma remain poor, with no approved agents available in this setting. Preclinical studies, however, suggest that MET inhibition or antiangiogenic agents may have efficacy in these diseases. These studies sought to evaluate the efficacy and safety of cabozantinib in advanced osteosarcoma and Ewing sarcoma.

The 2 multicenter, single-arm, 2-stage phase 2 trials treated 90 adults and children with advanced osteosarcoma or Ewing sarcoma with cabozantinib once daily until progressive disease or unacceptable toxicity. The primary end points were 6-month objective response (OR) and nonprogression in the osteosarcoma cohort and OR in the Ewing sarcoma cohort. 

The study is considered positive if 5 patients each with osteosarcoma or Ewing sarcoma experience an OR, or if 16 patients with osteosarcoma are free from progression at 6 months.

At baseline, the median age of study participants was 35 years and 33 years for the osteosarcoma and Ewing sarcoma cohorts, respectively, and the median lines of previous therapies was 3 and 4, respectively.

In the osteosarcoma cohort, 45.2% of patients experienced tumor shrinkage, including 11.9% who experienced partial responses (PRs) and 33.3% who saw disease stabilization. The 6-month nonprogression rate was 33.3%.

In the Ewing sarcoma cohort, tumor shrinkage occurred in 57.6% of patients, including 27.7% with PRs and 30.3% with disease stabilization. The 6-month nonprogression rate was 24.2%.

At least 1 adverse event occurred in 96% of patients.

The authors concluded that these data suggest that cabozantinib has “meaningful clinical activity in osteosarcoma and Ewing sarcoma patients with heavily pretreated advanced disease.” They noted that the primary end points were met in both cohorts.

Read more of Cancer Therapy Advisor's coverage of the ESMO 2018 meeting by visiting the conference page.

Reference

  1. Italiano A, Katz D, et al. Cabozantinib in patients with advanced osteosarcomas and Ewing sarcomas: a French Sarcoma Group (FSG)/US National Cancer Institute phase II collaborative study. Presented at: the ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract LBA67.

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