Long-Term Outcomes With PD-L1 Inhibition in Metastatic Urothelial Cancer


Key Points

  • Response was observed in 26% of patients, with a median duration of response of 22.1 months.
  • Treatment-related adverse events decreased in incidence after the first year of treatment.

As reported by Petrylak et al in JAMA Oncology, long-term follow-up of patients in a phase I study expansion cohort indicated enduring clinical benefit and maintained tolerability of atezolizumab (Tecentriq) in patients with metastatic urothelial carcinoma. 

Study Details

The study involved 95 evaluable patients enrolled at U.S. and European sites between March 2013 and August 2015 who received atezolizumab at 15 mg/kg or 1,200 mg every 3 weeks until unacceptable toxicity, protocol nonadherence, or loss of clinical benefit. Patients had a median age of 66 years, 76% were male, and 47% received atezolizumab as third-line or greater therapy.

Long-Term Outcomes

Median follow-up was 37.8 months (range = > 0.7–44.4 months). Response was observed in 25 patients (26%), including complete response in 9. Median duration of response was 22.1 months (range = 2.8 to > 41.0 months). Median progression-free survival was 2.7 months. Median overall survival was 10.1 months, with a 3-year rate of 27%. Response occurred in 40% of 40 patients with programmed cell death ligand 1 (PD-L1) expression of ≥ 5% tumor-infiltrating immune cells and 11% of 44 patients with expression < 5%. Median overall survival was 14.6 months and 7.6 months according to PD-L1 expression ≥ 5% and < 5%.

Grade 3 or 4 adverse events occurred in 53% of patients and were considered related to treatment in 9%. The most common treatment-related adverse events of any grade were fatigue (18%), asthenia (14%), decreased appetite (13%), and pruritus (13%). Treatment-related adverse events of any grade occurred in 66% of 95 patients during year 1 of treatment and in 41% of 37 patients receiving treatment beyond 1 year, including 35% of 37 patients in year 2, 28% of 25 patients in year 3, and 8% of 13 patients in year 4. Treatment-related adverse events led to treatment discontinuation in one patient (1%). No treatment-related deaths occurred.

The investigators concluded, “Atezolizumab remained well tolerated and provided durable clinical benefit to a heavily pretreated metastatic urothelial carcinoma population in this long-term study.”

The study was funded by F. Hoffmann–La Roche Ltd/Genentech, Inc.

Daniel P. Petrylak, MD, of Yale Cancer Center, is the corresponding author for the JAMA Oncology 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®.