In a phase II trial (Hoosier Cancer Research Network GU16-260) reported in the Journal of Clinical Oncology, Michael B. Atkins, MD, and colleagues found that nivolumab monotherapy was active in previously untreated patients with advanced clear cell renal carcinoma, particularly among those with favorable-risk disease, and that salvage nivolumab/ipilimumab showed little activity.
Michael B. Atkins, MD
Study Details
In the U.S. multicenter trial, 123 patients enrolled between May 2017 and December 2019 received nivolumab at 240 mg every 2 weeks for 12 weeks, then at 360 mg every 3 weeks for 12 weeks, followed by a dose of 480 mg every 4 weeks for a total of up to 96 weeks. Patients with progressive disease before or stable disease at 48 weeks could receive salvage nivolumab/ipilimumab; salvage therapy consisted of ipilimumab at 1 mg/kg every 3 weeks together with nivolumab at 3 mg/kg every 3 weeks for up to four doses, with the nivolumab dose reverting to 360 mg every 3 weeks for 12 weeks followed by 480 mg every 4 weeks after completion of treatment with ipilimumab. The primary endpoint was improvement in 1-year progression-free survival in patients with tumor PD-L1 expression of > 20% vs 0%.
Overall, 35 patients had favorable-risk, 76 had intermediate-risk, and 12 had poor-risk disease. Tumor PD-L1 expression status was 0% in 78 patients, ≥ 1% to ≤ 5% in 13, > 5% to ≤ 20% in 3, and > 20% in 8, with status unavailable for 21. Sarcomatoid features were present in 22 patients.
Key Findings
Among all patients, the objective response rate was 34.1% (95% confidence interval [CI] = 25.8%–43.2%), with rates of 57.1% in favorable-risk patients, 25.0% in intermediate-risk/poor-risk patients, and 36.4% in patients with sarcomatoid features. Rates were 26.9%, 50.0%, and 75.0% for patients with the PD-L1 expression of 0%, 1% to 20%, and 20%, respectively (P = .002 for trend). Median duration of response was 27.6 months (95% CI = 19.3 months–not reached), with 26 of 42 responders including 17 of 20 with favorable-risk disease remaining progression-free at time of analysis.
Progression-free survival at 1 year was 34.6% in the PD-L1 = 0% group vs 75.0% in the PD-L1 > 20% group (P = .050). Median progression-free survival was 8.3 months in the entire population, 32.5 months in patients with favorable-risk disease, and 5.4 and 5.2 months in those with intermediate- and poor-risk disease, respectively. Median progression-free survival was 7.7 months in patients with PD-L1 expression of 0% and 20.6 months in those with PD-L1 expression of > 20%.
A total of 97 patients with progressive disease or prolonged stable disease were potentially eligible for salvage nivolumab plus ipilimumab. Of these, 35 patients received treatment, with an objective response rate of 11.4% being observed.
Grade ≥ 3 treatment-related adverse events occurred in 35% of patients on nivolumab and 43% of those on salvage nivolumab/ipilimumab.
The investigators concluded, “Nivolumab monotherapy is active in treatment-naive [patients with] clear cell renal cell carcinoma. Although efficacy appears to be less than that of nivolumab/ipilimumab in patients with intermediate-risk/poor-risk disease, favorable-risk patients had notable benefit. Efficacy correlated with tumor PD-L1 status. Salvage nivolumab/ipilimumab was frequently not feasible and of limited benefit.”
Dr. Atkins, of Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and others. For full disclosures of the study authors, visit ascopubs.org.
