IMvigor211 Trial: Atezolizumab vs Chemotherapy in Platinum-Treated Advanced Urothelial Carcinoma
The phase III IMvigor211 trial showed no survival benefit for atezolizumab (Tecentriq) vs physician's choice of chemotherapy in platinum-treated locally advanced or metastatic urothelial carcinoma with programmed death-ligand 1 (PD-L1) expression ≥ 5%. Findings were reported in The Lancet by Powles et al.
Study Details
In the open-label trial, 931 patients with disease progression after platinum-based therapy from 198 sites primarily in Europe, North America, and the Asia-Pacific region were randomized between January 2015 and February 2016 to receive atezolizumab at 1,200 mg every 3 weeks (n = 467) or physician’s choice of chemotherapy (n = 464). Chemotherapy consisted of vinflunine at 320 mg/m2 (55% of patients), paclitaxel at 175 mg/m2 (33%), or docetaxel at 75 mg/m2 (12%) every 3 weeks.
Randomization was stratified by PD-L1 expression (expression on < 1% [IC0] or 1% to < 5% [IC1] of tumor-infiltrating immune cells vs ≥ 5% of tumor-infiltrating immune cells [IC2/3]), chemotherapy type, liver metastases, and number of prognostic factors. The primary endpoint was overall survival, tested hierarchically in prespecified populations—ie, IC2/3, followed by IC1/2/3, followed by the intention-to-treat population. A total of 234 patients (116 in the atezolizumab group, 118 in the chemotherapy group) were in the IC2/3 population.
Survival Outcomes
In the IC2/3 population, median overall survival was 11.1 months in the atezolizumab group vs 10.6 months in the chemotherapy group; the stratified hazard ratio (HR) was not significant (0.87, P = .41), precluding further formal statistical analysis. Confirmed objective response rates among evaluable patients in the IC2/3 population were 23% vs 22%, with median response durations of 15.9 months vs 8.3 months (HR = 0.57, 95% confidence interval [CI] = 0.26–1.26).
Median progression-free survival in the IC2/3 population was 2.4 months vs 4.2 months (HR = 1.01, 95% CI = 0.75–1.34). In exploratory analysis in the intent-to-treat population, overall survival at 12 months was 39.2% with atezolizumab and 32.4% with chemotherapy; median overall survival was 8.3 months with atezolizumab vs 7.5 months with taxanes and 9.2 months with vinflunine.
Adverse Events
In the intention-to-treat population, grade 3 or 4 treatment-related adverse events occurred in 20% of the atezolizumab group vs 43% of the chemotherapy group; the most common in the atezolizumab group were fatigue, anemia, and asthenia (2% each), and the most common in the chemotherapy group was neutropenia (11%). Adverse events led to discontinuation of treatment in 3% vs 14% of patients in the intent-to-treat population.
The investigators concluded, “Atezolizumab was not associated with significantly longer overall survival than chemotherapy in patients with platinum-refractory metastatic urothelial carcinoma overexpressing PD-L1 (IC2/3). However, the safety profile for atezolizumab was favourable compared with chemotherapy. Exploratory analysis of the intention-to-treat population showed well-tolerated, durable responses in line with previous phase II data for atezolizumab in this setting.”
The study was funded by F. Hoffmann-La Roche and Genentech.
Thomas Powles, MD, of Barts Cancer Institute, Queen Mary University of London, is the corresponding author for The Lancet article.
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