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

Presented by
Prof. Axel Merseburger, Prof. Jens Bedke
Conference
EAU 2019
Trial
Phase 3, SAUL, IMvigor211
In the Breaking News session, 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



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 diseaseb. 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.

Prof. Merseburger: “SAUL confirms the tolerability of atezolizumab in a ‘real-world’ UC and non-UC population. Efficacy in both the IMvigor211-like subgroup and the broader unselected population is consistent with previous anti-PD-L1/PD-1 pivotal UC trials. These results support use of atezolizumab in UC or non-UC, including patients with limited available treatment options.

Discussant Prof. Jens Bedke (University Hospital Tübingen, Germany) pointed out that advantages of this trial were its size and involvement of a heterogeneous patient group. He cautioned that while atezolizumab use yielded no increased toxicity, individual data in subgroups was still lacking, and he pointed to the early drops in curves on both arms of the trial. Prof. Bedke also mentioned the costs: €90-95,000 per patient. He concluded that while the data offers some insights, there is a strong need to identify patients that are most likely to benefit from atezolizumab.

Featured video:Prof. Bedke and Prof. Maria José Ribal (University of Barcelona, Spain) discussed the primary results from the SAUL study with Prof. Merseburger.

  1. Powles T et al. Lancet 2018;391:748-757.
  2. Sternberg et at. Eur Urol. 2019 Mar 22. pii: S0302-2838(19)30201-5.




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