Nivolumab has “limited intracranial activity” in patients with clear cell renal cell carcinoma (ccRCC) and previously untreated brain metastases, according to researchers.
In a phase 2 trial, nivolumab produced an intracranial response rate of 12% in ccRCC patients with previously untreated brain metastases.
The median intracranial progression-free survival (PFS) was longer among patients who had received prior focal therapy than among those with previously untreated brain metastases.
These results suggest “brain imaging and focal therapy should be considered before immune checkpoint inhibitors in patients with metastatic ccRCC,” Ronan Flippot, MD, of Université Paris-Saclay in Villejuif, France, and colleagues wrote in the.
Dr. Flippot and colleagues conducted this analysis of patients from the phase 2 GETUG-AFU 26 NIVOREN trial (). The researchers looked at 73 ccRCC patients with asymptomatic brain metastases who had received at least one prior line of antiangiogenic treatment.
Patients were divided into two cohorts. Cohort A included patients with previously untreated brain metastases (n = 39), and cohort B included patients who had received focal therapy for brain metastases (n = 34).
Baseline characteristics were similar between the cohorts. The median ages were 61 years in cohort A (range, 39-77) and 58 years in cohort B (range, 33-78). Most patients had grade 3-4 tumors (64% in cohort A and 78% in cohort B), and most had one brain lesion (67% and 59%, respectively). The median sum of the diameters of target lesions was 11 mm in cohort A and 17 mm in cohort B.
All patients received intravenous nivolumab at 3 mg/kg every 2 weeks until they progressed, developed unacceptable toxicity, died, withdrew consent, or the investigator stopped treatment.
The median follow-up was 23.6 months in cohort A and 20.2 months in cohort B. The median duration of treatment was 4.9 months and 4.5 months, respectively. Five patients in cohort A and four in cohort B were still receiving nivolumab at the data cutoff.
The primary endpoint was the intracranial response rate in cohort A, which was 12%. All four responders achieved a complete response. At baseline, all of them had grade 1-2 disease and a single brain lesion smaller than 1 cm.
Thirteen patients (38%) in cohort A had stable intracranial disease as their best response, and 17 (50%) had progressive intracranial disease. The remaining five patients could not be evaluated because they progressed and died before the first evaluation.
The extracranial response rate in cohort A was 21%, and all seven responders had partial responses. Ten patients had stable extracranial disease (30%), and 16 had extracranial progression (49%). The remaining six patients were not evaluable for extracranial response.
All four patients who achieved a complete intracranial response had a partial extracranial response. Six patients (18%) had discordant intracranial and extracranial responses.
The median intracranial PFS in cohort A was 2.7 months in cohort A versus 4.8 months in cohort B. When the researchers adjusted for baseline characteristics, they found that prior focal therapy decreased the risk of intracranial progression (hazard ratio, 0.49).
The median extracranial PFS was 2.8 months in cohort A versus 2.6 months in cohort B. The median global PFS was 2.4 months in cohort A versus 2.5 months in cohort B.
The overall survival rates at 12 months were 66.7% in cohort A and 58.8% in cohort B.
The most common treatment-related adverse events (in cohort A and B, respectively) were asthenia (21% and 24%) and rash (10% and 9%).
Grade 3/4 treatment-related adverse events occurred in four patients in cohort A and five in cohort B. In cohort A, these events were asthenia, elevated liver function tests, dyspnea, and atrioventricular block. In cohort B, the events were diarrhea, musculoskeletal pain, psoriasis, hypophosphatemia, and elevated creatinine (in two patients).
The patient who developed atrioventricular block permanently discontinued nivolumab. There were no other treatment-related adverse events that led to discontinuation.
This study was supported by Bristol-Myers Squibb. The researchers disclosed relationships with Bristol-Myers Squibb and many other companies.
SOURCE: Flippot R et al. .