Highlights from

EAU 2019

European Association of Urology annual congress

Barcelona 15-19 March 2019

Largest safety study of its kind with atezolizumab in patients with metastatic bladder cancer

In the Breaking News session on Monday 18 March, Prof. Axel Merseburger (University Hospital Schleswig-Holstein, Germany) announced the first results from SAUL, a phase 3b study evaluating the safety of atezolizumab in 997 patients with locally advanced or metastatic urothelial carcinoma (mUC) including several clinically relevant populations reflective of real-world clinical practice. Data from the study showed that both safety and efficacy, a secondary endpoint, were consistent with previous studies in both the overall population and a subgroup of patients corresponding to the patient population of the pivotal phase 3 study IMvigor211 (“IMvigor211-like”) [1].

SAUL is the largest prospective safety study of a cancer immunotherapy in mUC and provides information about atezolizumab in a real-world setting. This open label, single-arm, multicentre study was designed to assess the safety of atezolizumab as a second- to fourth-line treatment for people with locally advanced or mUC (95%) or non-urothelial carcinoma (5%) of the urinary tract. What makes this study unique is that it included patients with renal impairment, poor performance status (ECOG PS 2) [2], treated asymptomatic CNS metastases or stable controlled autoimmune disease, which have never been included in a study like this previously. The primary endpoint was safety; secondary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and duration of response (DoR).

The data presented at EAU show that the safety of the atezolizumab monotherapy treatment was consistent with the known safety profile of the medicine, even in this broad and complex patient group (see Table). Grade 3-4 adverse events (AEs) occurred in 43% of the patients, and treatment-related grade ≥3 AEs occurred in 13% of the patients, with most common reported side effects being fatigue, asthenia, colitis, and hypertension (each in 1%). AEs leading to treatment discontinuation occurred in 6% of the patients. Additionally, the efficacy results showed an OS of 10 months (95% CI 8.8–11.9 months) in the IMvigor211-like population. In the overall population, median OS was 8.7 months (95% CI 7.8–9.9). The median duration of follow up was 12.7 months.

Table – Adverse events in SAUL

Table SAUL study

a. Includes but not limited to patients with renal impairment, Eastern Cooperative Oncology Group (ECOG) performance status grade 2, treated asymptomatic central nervous system metastases or stable controlled autoimmune disease

b. All patients corresponding to the patient population in IMvigor211 (locally advanced or metastatic UC who have progressed during or following a platinum-containing regimen)

*Treatment-related grade 5 AEs (n=7, 0.7%): two cases of dyspnoea, one case each of colitis, intestinal perforation, respiratory failure, chronic kidney disease, drug-induced liver injury.

  1. Powles T et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018;391:748-757.
  2. Merseburger, A et al. Primary results from SAUL, a prospective multinational single-arm study of atezolizumab (atezo) for locally advanced or metastatic urothelial carcinoma (UC) or non-UC of the urinary tract. 2019, European Urology, in press

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.