IMmotion151: First-Line Atezolizumab/Bevacizumab vs Sunitinib in Metastatic Renal Cell Carcinoma
In the phase III IMmotion151 trial reported in The Lancet, Rini et al found that atezolizumab plus bevacizumab prolonged progression-free survival vs sunitinib in patients with previously untreated, programmed cell death ligand 1 (PD-L1)-positive, metastatic renal cell carcinoma.
Study Details
The open-label trial enrolled 915 patients with renal cell carcinoma with a component of clear cell or sarcomatoid histology from 152 sites in 21 countries (mainly in Europe, North America, and the Asia Pacific region). Patients were randomly assigned between May 2015 and October 2016 to receive atezolizumab at 1,200 mg plus bevacizumab at 15 mg/kg intravenously once every 3 weeks (n = 454) or sunitinib at 50 mg orally once daily for 4 weeks on, 2 weeks off (n = 461).
Co-primary endpoints were investigator-assessed progression-free survival in the PD-L1–positive population and overall survival in the intention-to-treat population. Overall, 362 patients (40%) had PD-L1–positive disease (≥ 1% tumor-infiltrating immune cells), including 178 in the atezolizumab/bevacizumab group and 184 in the sunitinib group.
Progression-Free and Overall Survival
The median follow-up was 15 months at the primary progression-free survival analysis and 24 months at the overall survival interim analysis. In the PD-L1–positive population, the median progression-free survival was 11.2 months in the atezolizumab/bevacizumab group vs 7.7 months in the sunitinib group (hazard ratio [HR] = 0.74, P = .0217). The median overall survival in the intention-to-treat population was 33.6 months vs 34.9 months (HR = 0.93, P = .4751); the overall survival results did not cross the significance boundary (α = .0076) at the interim analysis.
The median progression-free survival in the intention-to-treat population was 11.2 vs 8.4 months (HR = 0.83, P = .02190). At interim analysis, the median overall survival in the PD-L1–positive population was 34.0 months vs 32.7 months (HR = 0.84, P = .2857).
Adverse Events
Treatment-related grade 3 or 4 adverse events occurred in 40% of the atezolizumab/bevacizumab group and 54% of the sunitinib group, with the most common in both groups being hypertension (14% vs 17%). Treatment-related adverse events led to treatment discontinuation in 5% of the combination group vs 8% of the sunitinib group.
Five treatment-related deaths occurred in the atezolizumab/bevacizumab group vs one in the sunitinib group. The most common immune-mediated adverse events in the atezolizumab/bevacizumab group were rash, hypothyroidism, hyperthyroidism, and liver function test abnormalities; 16% of patients with immune-mediated adverse events received systemic corticosteroid treatment.
The investigators concluded, “Atezolizumab plus bevacizumab prolonged progression-free survival vs sunitinib in patients with metastatic renal cell carcinoma and showed a favorable safety profile. Longer-term follow-up is necessary to establish whether a survival benefit will emerge. These study results support atezolizumab plus bevacizumab as a first-line treatment option for selected patients with advanced renal cell carcinoma.”
Brian Rini, MD, of the Taussig Cancer Institute, Cleveland Clinic, is the corresponding author for The Lancet article.
Disclosure: The study was funded by F. Hoffmann–La Roche Ltd and Genentech Inc. For full disclosures of the study authors, visit thelancet.com.
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