Intracranial Response Achieved by Cabozantinib in mRCC | Targeted oncology

Patients with metastatic renal cell carcinoma (RCC) with brain metastases benefited from treatment with cabozantinib (Cabometyx), according to findings from a retrospective study presented at the 2021 Genitourinary Cancer Symposium.

Results showed that, in patients with uncontrolled baseline brain metastases (n = 25) who received cabozantinib, the intracranial response rate was 61% (95% CI, 39% –80%); this included an overall response rate of 13% (CR) and a partial response rate of 48% (PR). Thirty percent and 9% of patients had chronic disease (SD) and advanced disease (PD), respectively.

In those who had controlled brain disease at baseline (n = 44), the intracranial response rate was 57% (95% CI, 41% –72%), which included all PR. SD and PD rates were at 31% and 12%, respectively.

“This is the largest group of patients with metastatic RCC with concomitant brain metastases treated with cabozantinib,” lead study author Laure Hirsch, MD, of the Department of Medical Oncology, Cochin Hospital, University of Paris Descartes, said in Paris, France. poster display of the data. “Cabozantinib was associated with high intracranial activity with a high response rate in patients with uncontrolled intracranial infection.”

The FDA approved cabozantinib in December 2017 as a treatment for patients who had not previously been treated with advanced RCC. Recently, in January 2021, the FDA approved the combination of nivolumab (Opdivo) as well as cabozantinib for the facial treatment of patients with advanced RCC.

In the multicenter, an international analysis, researchers identified 69 patients with metastatic RCC and brain metastases across 15 institutions treated with single-agent cabozantinib. The trial was extended in 2 cohorts: those with progressive intracranial metastases (n = 25) and those with non-progressive / controlled intracranial metastases (n = 44).

Eighty-seven percent of patients were identified as International RCC Metastatic Database Consortium or severe risk, and 75% had received cabozantinib in the second or later line. Sixty-five percent of patients in cohort 1 received prior brain-guided treatment, such as radiation or surgery, versus 93% of patients in cohort 2.

At the time of the analysis, 23% of patients were still being treated; 52% had stopped due to disease progression, and 9% had stopped treatment for toxic-related reasons.

Intracranial and extracranial responses were evaluated with RECIST v1.1 criteria.

Additional data showed that the external response rate was 52% and 41%, respectively, in cohorts 1 and 2. There were two non-valuable patients in each group because lesion sizes were less than 5 mm.

In cohort 1, the median failure to treatment (TTF) was 9.9 months (95% CI, 5.9–14.0) and the overall survival rate (OS) was 14.7 months (95% CI, 7.7–23). ). In cohort 2, the median TFF and OS were 9.0 months (95% CI, 4.6–11.4) and 14.1 months (95% CI, 11.0–22.0), respectively.

Researchers also measured the frequency of brain progression and brain safety. In cohort 1, 16% (95% CI, 4% –33%) of patients had brain disease progression compared with 9% (95% CI, 3% –12%) in cohort 2.

In terms of safety, no adverse events (AEs) were reported; the most common AEs included muscle weakness (79%), diarrhea (46%), and nausea (32%). Nine patients (13%) experienced level 3/4 AE, but no neurological toxins were observed. Thirty-eight patients (55%) wanted dose reductions.

Hirsch noted that a moderate review of images and adding more patients to this test is ongoing.

The continuous, prospective, multicenter, CABRAMETtrial phase 2 (NCT03967522) evaluates the safety and efficacy of cabozantinib in patients with metastatic RCC with brain metastases. In addition, the COSMIC 313 level 3 trial (NCT03393337219) looks at the combination of cabozantinib plus nivolumab and ipilimumab (Yervoy) in patients not previously treated with advanced RCC, including those with brain metastases.


Hirsch L, Chanza NM, Farah S, et al. Activity and safety of cabozantinib (cabo) in brain metastases (BM) from metastatic renal cell carcinoma (mRCC): An international multicenter study. J Clin Oncol. 2021; 39 (solair 6): 310. doi: 10.1200 / JCO.2021.39.6_suppl.310