IMvigor211 Trial: Atezolizumab vs Chemotherapy in Platinum-Treated Advanced Urothelial Carcinoma


Key Points

  • Atezolizumab did not improve overall survival vs chemotherapy in patients with PD-L1 expression ≥ 5%.
  • Atezolizumab was associated with fewer severe adverse events.

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. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.