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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

Sternberg, Cora N., Loriot, Yohann, James, Nicholas, Choy, Ernest, Castellano, Daniel, Lopez-Rios, Fernando, Banna, Giuseppe L., De Giorgi, Ugo, Masini, Cristina, Bamias, Aristotelis, Garcia del Muro, Xavier, Duran, Ignacio, Powles, Thomas, Gamulin, Marija, Zengerling, Friedemann, Geczi, Lajos, Gedye, Craig, de Ducla, Sabine, Fear, Simon and Merseburger, Axel S. 2019. 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. European Urology 10.1016/j.eururo.2019.03.015

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Abstract

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 12.7 mo), 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 (Clinicaltrials.gov: NCT02928406). Intervention Atezolizumab 1200 mg every 3 wk 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 2.8 mo (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 8.7 mo (95% confidence interval [CI] 7.8–9.9). The 6-mo OS rate was 60% (95% CI 57–63%), median PFS was 2.2 mo (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 10.0 mo (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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0302-2838
Date of First Compliant Deposit: 3 April 2019
Date of Acceptance: 13 March 2019
Last Modified: 03 Apr 2019 12:37
URI: http://orca.cf.ac.uk/id/eprint/121360

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