Background
Phase III RCT of 886 patients with treatment-naïve advanced clear-cell RCC with ≥1 measurable lesion; co-primary endpoints assessed in the PD-L1-positive population.
Interventions and follow up
Arm A: Avelumab 10mg/kg IV q2wk + axitinib 5mg PO BID
Arm B: Sunitinib 50mg 4wk on, 2wk off
Primary endpoint: PFS and OS in PD-L1-positive population
Median follow-up: minimum 13mo
Arm B: Sunitinib 50mg 4wk on, 2wk off
Primary endpoint: PFS and OS in PD-L1-positive population
Median follow-up: minimum 13mo
Results
mPFS, PD-L1+: 13.8mo vs 7.0mo, HR 0.62, 95%CI 0.49-0.77
mPFS, overall population: 13.3mo vs 8.0mo, HR 0.69, 95%CI 0.57-0.82
PFS, favorable risk: HR 0.54, 95%CI 0.32-0.91; ORR 68% vs 38%
PFS, intermediate risk: HR 0.74, 95%CI 0.57-0.95
PFS, poor risk: HR 0.57, 95%CI 0.38-0.88
OS: immature at this analysis
mPFS, overall population: 13.3mo vs 8.0mo, HR 0.69, 95%CI 0.57-0.82
PFS, favorable risk: HR 0.54, 95%CI 0.32-0.91; ORR 68% vs 38%
PFS, intermediate risk: HR 0.74, 95%CI 0.57-0.95
PFS, poor risk: HR 0.57, 95%CI 0.38-0.88
OS: immature at this analysis
Adverse events
Grade 3-4 treatment-related (A vs B): 71.2% vs 71.5%; hypertension most common grade ≥3 event
Discontinuation due to AEs (combination): 22.8%
Discontinuation due to AEs (combination): 22.8%
Conclusions
First-line avelumab + axitinib improved PFS across all IMDC risk groups versus sunitinib in advanced RCC.
Key Limitations
Open-label design; OS immature with no demonstrated survival benefit in subsequent analyses, limiting positioning relative to OS-positive IO-TKI and IO-IO regimens; PD-L1 stratification of uncertain clinical utility.
Clinical Context
FDA approved avelumab + axitinib (May 2019) for first-line advanced RCC; EMA approval followed. ESMO lists it as an option, though absence of mature OS benefit has favored OS-positive doublets in practice.