Activity of Cabozantinib in Radioresistant Brain Metastases From Renal Cell Carcinoma

Two Case Reports

Sylvie Négrier; Guillaume Moriceau; Valéry Attignon; Véronique Haddad; Daniel Pissaloux; Nicole Guerin; Christian Carrie

Disclosures

J Med Case Reports. 2018;12(351) 

In This Article

Background

Renal carcinoma represents 3–5% of the incidence of adult malign tumors. The more common histologic subtype is clear cell carcinoma and it accounts for more than 75% of cases; several minor subtypes are diagnosed among the remaining 25% of cases. Papillary carcinoma, type I or II, is the most frequent of these minor subtypes and accounts for 10% of all cases. Surgery with partial or radical nephrectomies cures most patients and disease-specific survival at 5 years is between 70 and 80%.[1,2] Metastases often occur in the 2 to 5 years following surgery but are uncommon at initial diagnosis. Metastases are frequently located in lungs and lymph nodes, but also in bones and liver; brain metastases are unfrequently observed with an estimated incidence of 10%.[3,4] Brain metastases are generally associated with a limited survival time despite local specific treatments with neurosurgery or radiation therapy.[3,5] Significant progress in the treatment of metastatic renal cell carcinoma (mRCC) was achieved in the past decade; however, patients die after a survival period varying from 1 to 3–4 years depending on the prognosis factors.[1] Due to specific gene alterations, the vascular endothelial growth factor (VEGF) pathway is a major driver of clear cell renal carcinoma development, which is the most frequent histologic subtype, and, as a consequence, VEGF or VEGF receptor (VEGFr) inhibitors are key in the treatment of these patients.[1] Other genes, especially MET, involved in the carcinogenesis of a number of tumors, were also found to be determinants for tumor progression and resistance to treatments. MET was first identified as a major driver for the development of papillary renal carcinoma, but was also shown to be involved in resistant clear cell carcinomas.[6–8] Different MET or dual MET and VEGF-targeted therapies were recently investigated through clinical trials.[9,10] One of the most recently registered targeted therapies for the treatment of mRCC, cabozantinib, is a tyrosine kinase inhibitor (TKI) directed against VEGFrs, but also against other different genes: c-Met, RET, and AXL.[11]

We describe two cases of mRCC who developed resistant brain metastases despite several systemic treatments as well as stereotaxic radiation. Cabozantinib induced significant tumor reductions including the life-threatening brain metastases.

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