Background
Phase III RCT (N=821) of advanced or metastatic clear-cell RCC previously treated with one or two prior antiangiogenic regimens (second-line setting).
Interventions and follow up
Arm A: Nivolumab 3mg/kg IV q2wk
Arm B: Everolimus 10mg PO daily
Primary endpoint: OS
Median follow-up: ~14mo (minimum)
Arm B: Everolimus 10mg PO daily
Primary endpoint: OS
Median follow-up: ~14mo (minimum)
Results
mOS (A vs B): 25.0mo vs 19.6mo; HR 0.73, 98.5% CI 0.57-0.93, P=.002
mPFS (A vs B): 4.6mo vs 4.4mo; HR 0.88, 95% CI 0.75-1.03, P=.11
ORR (A vs B): 25% vs 5%; OR 5.98, 95% CI 3.68-9.72, P<.001
mPFS (A vs B): 4.6mo vs 4.4mo; HR 0.88, 95% CI 0.75-1.03, P=.11
ORR (A vs B): 25% vs 5%; OR 5.98, 95% CI 3.68-9.72, P<.001
Adverse events
Grade 3-4 treatment-related AEs (A vs B): 19% vs 37%
Most common with nivolumab: fatigue, nausea, pruritus; most common with everolimus: fatigue, anemia, stomatitis
Most common with nivolumab: fatigue, nausea, pruritus; most common with everolimus: fatigue, anemia, stomatitis
Conclusions
Nivolumab significantly improved OS with a more favorable toxicity profile versus everolimus in previously treated advanced clear-cell RCC.
Key Limitations
PFS was not improved despite the OS benefit; trial restricted to clear-cell histology and to patients with prior antiangiogenic therapy; everolimus comparator now less commonly used first after TKI.
Clinical Context
FDA approved nivolumab (Nov 2015) for advanced RCC after prior antiangiogenic therapy, the first immune-checkpoint approval in RCC. Established PD-1 blockade in the second-line setting per ASCO/ESMO; subsequently largely superseded by first-line IO-based combinations.