Nivolumab Trial Failure Raises the Question of Brain Imaging in Kidney Cancer

Nivolumab had limited efficacy against previously untreated brain metastases in patients with metastatic renal cell carcinoma (RCC), according to the recently published results of the GETUG-AFU 26 NIVOREN trial. Although the trial results were negative and do not necessarily impact clinical practice, they do raise the question of whether brain imaging should be routinely performed in patients with metastatic RCC. About 10% of patients with metastatic RCC develop brain metastasis.

“One of the hardest things to treat in patients with metastatic kidney cancer are brain metastases,” said Che-Kai Tsao, MD, medical director of the Ruttenberg Treatment Center at the Tisch Cancer Institute at Mount Sinai, during an interview with Cancer Network. “There is a lot of controversy about the best way to treat these patients.”

The phase II multicenter trial included patients with metastatic clear cell RCC whose disease progressed during first-line treatment with vascular endothelial growth factor (VEGF)-directed therapies. All patients had asymptomatic brain metastases, which were prospectively found via brain imaging, and all received nivolumab monotherapy.

Patients were grouped depending on whether they received prior therapy for brain metastases. Cohort A did not receive prior focal brain therapy, and cohort B did receive prior focal brain therapy. Intracranial response for patients with previously untreated brain metastases in cohort A was the primary study endpoint.

A total of 729 patients were enrolled, of which 76 (10.4%) had brain metastases at baseline. Overall, 73 patients with brain metastasis were treated with nivolumab, which included 39 patients with previously untreated brain metastases in cohort A and 34 patients with previously treated brain metastases in cohort B. The majority of patients (88%) in cohort B underwent stereotactic radiotherapy as their prior focal brain therapy.

Only 4 of the 39 patients with previously untreated brain metastases in cohort A had an intracranial objective response, all of which were confirmed complete responses. All 4 patients lacked multiple lesions and the single lesion found was smaller than 1 cm; they also all had an extracranial response. The median duration of response for these intracranial responders was 7.2 months (95% CI, 3.2 months–not estimable), and 2 had ongoing responses at last follow-up.

The median intracranial progression–free survival was shorter for the patients with previously untreated brain metastases in cohort A compared with those in cohort B (2.7 vs 4.8 months), with double the likelihood of intracranial progression (hazard ratio [HR], 2.04; 95% CI, 1.08–3.83). The 6-month overall survival rate was about 70% in both cohorts.

“These data clearly tell us that efficacy is very limited,” said Tsao. He said the authors “make a good claim” that nivolumab can potentially be effective when the disease is detected relatively early and is smaller in size, but ultimately, nivolumab should not replace the standard of care for brain metastasis in metastatic RCC, which is generally radiation.

In light of the trial results, the study authors suggest that brain imaging, which is not standard practice in the clinic for patients with metastatic RCC, may allow the detection of brain lesions earlier, when they are more amenable to treatment.

“That’s certainly a question to be explored,” said Tsao. He noted that while brain imaging is not standard practice in metastatic RCC, it is in other cancer types like lung cancer, because there is a high incidence of brain metastasis.