EAU 2019: Primary Results from SAUL: A Prospective, Multinational Single-Arm Study of Atezolizumab for Locally Advanced or Metastatic Urothelial Carcinoma of the Urinary Tract

Barcelona, Spain (UroToday.com) Dr. Axel Merseburger presented the preliminary results of the Safety of Atezolizumab in locally advanced or metastatic UrotheliaL and non-urothelial carcinoma of the urinary tract (SAUL) study at the EAU 2019 Breaking News session. Atezolizumab is a humanized monoclonal antibody that targets PD-L1 and inhibits the interaction with PD-L1 receptors. This treatment was approved as monotherapy for patients with locally advanced or metastatic urothelial carcinoma1-3:

  • After platinum-containing chemotherapy, or
  • Considered cisplatin ineligible and PD-L1 positive, or
  • Ineligible for any platinum therapy, irrespective of PD-L1 status (US only)
SAUL enrolled a broad patient population with pretreated locally advanced/metastatic urinary tract carcinoma, treating them with atezolizumab 12 mg IV q 3 weeks until loss of clinical benefit, unacceptable toxicity, patient or investigator decision to withdraw from therapy or death. The primary endpoint was safety; between November 30, 2016 and March 16, 2018, there were 1,004 patients recruited, with 997 treated patients enrolled in over 32 countries:
EAU 2019_SAUL_1a.png

The median patient age was 68 (range 34-93), 77% were male, 47% of patients were ECOG 1 and 10% ECOG 2, 38% of patients had no prior treatment, 54% had 1 prior treatment, and 28% were PD-L1 positive. The majority of tumors were urothelial carcinoma (95%), 75% were in the bladder, 12% in the renal pelvis and 10% in the ureter.

The adverse event profile was consistent with previous IO trials. The rate of any treatment-related adverse events was 53%; the most common specific adverse events were asthenia and fatigue. In the ITT population (n=1,004), the median overall survival (OS) was 8.7 months (95%CI 7.8-9.9), the 6-month OS rate was 60% (95%CI 57-63%), and the 12-month OS rate was 41% (95%CI 38-44%). The median PFS in the ITT population was 2.2 months (95%CI 2.1-2.4), 6-month PFS rate was 29% (95%CI 26-32%), and the 12-month PFS rate was 17% (95%CI 15-20%). The objective response rate was 13% (95%CI 11-16%), with 3% of patients having a complete response, 11% partial response, 26% stable disease, and a disease control rate of 40%. There were 6% of patients that received treatment and discontinued secondary to an adverse event.

In a subgroup analysis assessing patients that would have been candidates for the phase 3 randomized controlled trial IMvigor211 (n=643)3, the median OS was 10.0 months (95%CI 8.8-11.9) and the 12-month OS rate was 46% (95%CI 41-50%). The median PFS was 2.3 months (95%CI 2.2-2.6), and the objective response rate was 14% (95%CI 11-17%). Similarly, when comparing SAUL to other criteria/trials, Dr. Merseburger notes that these OS curves are nearly identical:
EAU 2019_SAUL_1b.png

Dr. Merseburger concluded his presentation of the preliminary results of SAUL with several take-home messages:
  • SAUL is the largest prospective clinical trial of immunotherapy in advanced urinary tract carcinoma
  • Atezolizumab is a tolerable and effective treatment, even in complex comorbid populations
  • The efficacy overall and in the IMvigor211-like subgroup is consistent with previous pivotal anti-PD-L1/PD-1 urothelial carcinoma trials: the median OS in SAUL was 10.0 months in the IMvigor211-like population (n=643) and 8.7 months in the ITT population (n=1,004)
  • These results support the use of atezolizumab in urinary tract carcinoma, including in patients with limited treatment options
This paper has been accepted to European Urology and will be available in press soon.

Presented by: Axel S. Merseburger, MD, Chairman of the Department of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia, Twitter: @zklaassen_md  at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019. 

  1. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet 2016;387(10031):1909-1920.
  2. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: A single-arm, multicentre, phase 2 trial. Lancet 2017;389(10064):67-76.
  3. Powles T, Duran I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): A multicentre, open-label, phase 3 randomized controlled trial. Lancet 2018;391:748-757.