Two children with recurrent metastatic, TFE3 fusion-positive, clear-cell renal cell carcinoma (RCC) tumors that expressed MET  experienced “prolonged disease control” following treatment with cabozantinib, according to a pair of case reports published in Pediatric Blood & Cancer.1

“Both patients had significant disease regression and symptomatic improvement for over 15 months with tolerable adverse effects,” reported the authors.

Cabozantinib, a tyrosine kinase inhibitor, targets MET as well as VEGFR2 and RET. It has been approved by the US Food and Drug Administration (FDA) as a second-line therapy for RCC in adults and was granted orphan drug status by the FDA in 2011.

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Both children — a 16-year-old girl and a 12-year-old boy — had stage IV, TFE3 fusion-positive, clear-cell RCC at diagnosis. Chart reviews were conducted for their records dating from 2013 to 2016.

Both children returned to “normal activities of daily living” but the girl’s disease returned by 17 months of treatment and she died. Her pain symptoms “markedly improved” over 4 weeks following 60 mg orally daily cabozantinib and a pleural drain to address respiratory distress. On imaging, “many metastases” had regressed during treatment but new liver metastases had appeared.

Following radiotherapy for painful vertebral metastases, the boy experienced pain resolution within 3 months of starting adjuvant cabozantinib (60 mg orally daily).

“At last follow-up, he has remained without disease progression and with excellent symptom control for 18 months,” the authors reported.

Previous to the new case studies, there were “no published data on its use” for pediatric RCC, in part because of the rarity of the disease, the authors noted.

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The Children’s Oncology Group is conducting a phase 1 trial of cabozantinib for pediatric solid tumors, the authors noted. “Our experience suggests cabozantinib is useful in the management of TFE3 fusion-positive, MET-expressing pediatric RCC, at a dosing similar to that proposed from the preliminary data of the phase 1 trial,” they reported.


  1. Wedekind MF, Ranalli M, Shah N. Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal cell carcinoma. Pediatr Blood Cancer. 2017 Apr 18. doi: 10.1002/pbc.26586 [Epub ahead of print]