Primary Results from SAUL, a Multinational Single-arm Safety Study of Atezolizumab Therapy for Locally Advanced or Metastatic Urothelial or Nonurothelial Carcinoma of the Urinary Tract

Eur Urol. 2019 Jul;76(1):73-81. doi: 10.1016/j.eururo.2019.03.015. Epub 2019 Mar 23.


Background: Atezolizumab, a humanised monoclonal antibody targeting PD-L1, is approved for locally advanced/metastatic urothelial carcinoma. SAUL evaluated atezolizumab in a broader, pretreated population, including patients ineligible for the pivotal IMvigor211 phase 3 trial of atezolizumab.

Objective: To determine the safety and efficacy of atezolizumab in an international real-world setting.

Design, setting, and participants: Between November 2016 and March 2018 (median follow-up 12.7mo), 1004 patients with locally advanced or metastatic urothelial or nonurothelial urinary tract carcinoma who experienced progression during or after one to three prior therapies for inoperable, locally advanced, or metastatic disease were enrolled. Patients with renal impairment, treated central nervous system metastases, or stable controlled autoimmune disease were eligible; 10% had Eastern Cooperative Oncology Group performance status (ECOG PS) 2 and 98% were platinum pretreated ( NCT02928406).

Intervention: Atezolizumab 1200mg every 3wk until progression or unacceptable toxicity.

Outcome measurements and statistical analysis: The primary endpoint was safety. Secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR).

Results and limitations: The median treatment duration was 2.8mo (range 0-19); 22% remained on treatment and 8% discontinued because of toxicity. Grade ≥3 adverse events occurred in 45% of patients. The most common grade ≥3 treatment-related adverse events were fatigue, asthenia, colitis, and hypertension (each in 1%). Median OS was 8.7mo (95% confidence interval [CI] 7.8-9.9). The 6-mo OS rate was 60% (95% CI 57-63%), median PFS was 2.2mo (95% CI 2.1-2.4), and the ORR was 13% (95% CI 11-16%; 3% complete responses). Among IMvigor211-like patients (excluding ECOG PS 2 and other IMvigor211 exclusion criteria), median OS was 10.0mo (95% CI 8.8-11.9) and 6-mo OS was 65% (95% CI 61-69%).

Conclusions: SAUL confirms the tolerability of atezolizumab in a real-world pretreated population with urinary tract carcinoma. Efficacy overall and in the IMvigor211-like subgroup is consistent with previous pivotal anti-PD-L1/PD-1 urothelial carcinoma trials. These results support the use of atezolizumab in urinary tract carcinoma, including patients with limited treatment options.

Patient summary: In this international study we investigated the efficacy and safety of atezolizumab treatment for advanced urinary tract cancer in a large population of pretreated patients, including those who would not normally be candidates for clinical trials. Patients tolerated the treatment well, even if they had autoimmune disease, were being treated with corticosteroids, or had disease that had spread to their brain. Life expectancy in this study for patients typical of everyday clinical practice was similar to that seen in trials that enrolled only selected fitter patients.

Keywords: Atezolizumab; Autoimmune disease; Central nervous system metastases; Immunotherapy; Nonurothelial carcinoma; PD-L1; Real world; Steroid; Urothelial carcinoma.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anemia / chemically induced
  • Anorexia / chemically induced
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Asthenia / chemically induced
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / secondary
  • Colitis / chemically induced
  • Disease Progression
  • Fatigue / chemically induced
  • Female
  • Humans
  • Hypertension / chemically induced
  • Male
  • Middle Aged
  • Progression-Free Survival
  • Retreatment
  • Survival Rate
  • Urinary Tract Infections / chemically induced
  • Urologic Neoplasms / drug therapy*
  • Urologic Neoplasms / pathology*


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • atezolizumab

Associated data