Atezolizumab Shows Activity in First-Line Treatment of Cisplatin-Ineligible Patients With Advanced Urothelial Carcinoma


Key Points

  • Atezolizumab produced durable responses in the first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma.
  • Responses were observed across all PD-L1 expression subgroups.

In a phase II trial reported in The Lancet, Balar et al found that first-line atezolizumab (Tecentriq) produced durable responses in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma.

In the study, 119 patients from 47 sites in North America and Europe who were ineligible for cisplatin treatment received atezolizumab at 1,200 mg every 21 days until disease progression. The primary endpoint was independently confirmed objective response rate in programmed cell death ligand 1 (PD-L1) expression subgroups and in all patients.

Response Rates

Median follow-up was 17.2 months. Objective response was observed in 27 patients (23%, 95% confidence interval = 16%–31%), including complete response in 11 patients (9%). Median response duration was not reached; 19 responses were ongoing at the time of analysis. Response rates were 28% in 32 patients with PD-L1 expression on ≥ 5% of tumor-infiltrating immune cells, 24% in 80 patients with ≥ 1% expression, 21% in 48 patients with ≥ 1% and < 5% expression, and 21% in 39 patients with < 1% expression. Median progression-free survival was 2.7 months. Median overall survival was 15.9 months. Response was associated with tumor mutation load.

Adverse Events

The most common treatment-related adverse events were fatigue (30%), diarrhea (12%), and pruritus (11%). Grade 3 or 4 treatment-related adverse events occurred in 16% of patients, with the most common being fatigue, increased alanine transaminase, and increased aspartate transaminase (3% each). Adverse events led to discontinuation of treatment in 8% of patients. Immune-mediated adverse events occurred in 12%. One death, due to sepsis, was considered related to treatment.

The investigators concluded: “Atezolizumab showed encouraging durable response rates, survival, and tolerability, supporting its therapeutic use in untreated metastatic urothelial cancer.”

The study was funded by F. Hoffmann-La Roche and Genentech.

Arjun V. Balar, MD, of NYU Langone Medical Center Perlmutter Cancer Center, is the corresponding author of The Lancet article.

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