Local treatment preferred option for brain metastases from renal cell carcinoma

Bernard Escudier

MIAMI — Brain metastases from renal cell carcinoma have negative prognostic implications, and the number and size of those metastases greatly influence outcomes, according to according to a presenter at International Kidney Cancer Symposium.

Local treatment is recommended when possible, and stereotactic radiotherapy is the preferred option, Bernard Escudier, MD, former chair of the genitourinary group at Institut Gustave Roussy in Villejuif, France, said during a presentation.

“Brain metastases are not uncommon in renal cell carcinoma,” Escudier said. “They are often are asymptomatic and found during screening, including brain imaging, but they sometimes are large and symptomatic.”

Prior studies suggest incidence of brain metastases from renal cell carcinoma ranges from 6% to 10%. These metastases are associated with poor outcomes.

A study by Grassi and colleagues, published in 2014 in Future Oncology, showed median OS was 20.2 months for patients with brain metastases and 25 months for those without. A study by Shuto and colleagues, published in 2010 in Journal of Neuro-Oncology, showed median OS of 2.1 years for patients who had brain metastases surgically resected and 0.7 years for patients who did not undergo resection.

A study by Schuch and colleagues, published in 2008 in Cancer, showed risk for central nervous system recurrence was significantly higher among patients who underwent treatment for two or more brain metastases than those who had one brain metastasis (P <.001).

Local treatment is the preferred option, Escudier said.

“Radiation therapy is effective and can replace surgery,” he said.

Tumor control increases with a single dose of stereotactic radiotherapy compared with fractionated doses, Escudier said.

Also, patients with a single metastasis fare better than those with multiple metastases, and local control decreases with the size of the lesions, he added. Results of several series showed the maximum size for good local control is 2 cm to 2.5 cm, and a 3-cm lesion is the highest size for stereotactic radio therapy, Escudier said.

Escudier also summarized data related to medical treatment of brain metastases from renal cell carcinoma.

Tyrosine kinase inhibitors have little activity in this setting. Chevreau and colleagues analyzed 16 patients with previously untreated brain metastases who received sunitinib (Sutent, Pfizer). No patients responded to treatment; median PFS was 2.3 months and median OS was 6 months.

The Nivoren study, results of which were presented at this year’s Genitourinary Cancer Symposium, assessed the effect of the PD-1 inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) for 55 patients with one (67%), two (12%) or more than two (21%) brain metastases.

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The majority (67%) of patients had undergone no prior treatment for their brain metastases, whereas 9% had undergone surgery and 31% received brain radiotherapy.

Ten patients (23%) achieved objective response to nivolumab treatment and 21 (48%) exhibited local progression. Researchers observed no responses in treatment-naive brain metastases.

Results suggested “rapid flare-up” on brain metastases can occur, and brain metastases should be treated locally prior to initiation of nivolumab treatment, Escudier said.

Early clinical experience suggests there is “a strong rationale” for use of cabozantinib (Cabometyx, Exelixis) — a small molecule inhibitor of the MET, AXL and VEGFR2 tyrosine kinases — but data are still limited, Escudier said. – by Mark Leiser

For more information:

Escudier B. How should we treat brain metastases from RCC? Presented at: International Kidney Cancer Symposium; Nov. 3-4, 2017; Miami.

Disclosure: Escudier reports honorarium from Bayer, Bristol-Myers Squibb, Calithera, Eisai, Exelixis, Ipsen, Novartis, Pfizer and Roche; and travel grants/support and research grants from Bristol-Myers Squibb, Novartis and Pfizer.