Background
Phase III RCT of 915 patients with treatment-naïve clear-cell or sarcomatoid metastatic RCC (MSKCC favorable 20%, intermediate 69%, poor 12%).
Interventions and follow up
Arm A: Atezolizumab 1200mg + bevacizumab 15mg/kg IV q3w
Arm B: Sunitinib 50mg 4wk on, 2wk off
Primary endpoint: PFS in PD-L1-positive population and OS in ITT
Median follow-up: 15mo for PFS, 24mo for OS analysis
Arm B: Sunitinib 50mg 4wk on, 2wk off
Primary endpoint: PFS in PD-L1-positive population and OS in ITT
Median follow-up: 15mo for PFS, 24mo for OS analysis
Results
mPFS, PD-L1-positive (A vs B): 11.2mo vs 7.7mo, HR 0.74, 95%CI 0.57-0.96, P=.0217
mOS, ITT: HR 0.93, 95%CI 0.76-1.14, did not cross significance boundary at interim analysis
mOS, ITT: HR 0.93, 95%CI 0.76-1.14, did not cross significance boundary at interim analysis
Adverse events
Grade 3-4 (A vs B): 40% vs 54%; treatment discontinuations 5% vs 8%
Selected events (A vs B): hypertension 14% vs 17%, thrombocytopenia 0% vs 5%; proteinuria common with combination
Selected events (A vs B): hypertension 14% vs 17%, thrombocytopenia 0% vs 5%; proteinuria common with combination
Conclusions
First-line atezolizumab + bevacizumab improved PFS in PD-L1-positive treatment-naïve metastatic RCC, with a favorable safety profile.
Key Limitations
Open-label design; OS in ITT not statistically significant; modest PFS gain confined to PD-L1-positive subgroup. The regimen did not gain regulatory approval in RCC and is not used in routine practice.
Clinical Context
Atezolizumab + bevacizumab was not FDA- or EMA-approved for RCC given the lack of significant OS benefit. ESMO guidelines favor OS-positive IO-TKI and IO-IO combinations for first-line advanced clear-cell RCC.