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

Discussion

To the best of our knowledge, this is one the two first reports of efficacy of cabozantinib in brain metastases of RCC. Cabozantinib is a TKI directed against VEGFrs as well as MET, RET and AXL gene expression.[11,13] Cabozantinib was approved by both the US Food and Drug Administration and the European Medicines Agency in 2016 for the treatment of mRCC after failure of previous treatments with angiogenesis inhibitors. In fact, cabozantinib was shown to improve progression-free survival (PFS) and overall survival over everolimus in patients with advanced or mRCC.[11,14] More recently, PFS with cabozantinib was found superior to sunitinib in patients with non-pretreated mRCC in a randomized phase 2 trial.[15] None of these trials enrolled patients with active brain metastases; as a consequence, the potential efficacy of cabozantinib is unknown at this specific tumor site. After a review of the literature, we found a case report on the regression of brain metastases in a patient with RCC and one non-small cell lung carcinoma (NSCLC) under cabozantinib.[16,17] These cases demonstrated the potential activity of cabozantinib on the brain, which is an unfavorable site in all patients with metastases. In addition, our two cases demonstrate the potential efficacy of cabozantinib in radioresistant brain metastases of RCC. Some retrospective analyses reported some tumor regression in brain metastases under other VEGFr inhibitors, mostly sunitinib, but efficacy appeared limited when investigated in a specific trial.[3,18,19] A hypothesis of a correlation between the effect of cabozantinib on resistant brain metastases and MET inhibition can be raised. In our first case, cMet was found mutated and the second case has a papillary carcinoma which is known to commonly have MET gene alterations, although no mutation in this gene was found in the tumor of this patient.[6,20] Notably, a MET mutation was present in the case of NSCLC with brain metastases successfully treated by cabozantinib.[17] Recently, some results indicated more frequent MET gene mutations or overexpression in brain metastases of patients with mRCC compared to primary tumor or other metastatic sites.[21,22]

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