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.

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.

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

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).

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

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

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%).

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.

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.

European urology. 2019 Mar 22 [Epub ahead of print]

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

San Camillo and Forlanini Hospitals, Rome, Italy. Electronic address: ., Department of Cancer Medicine and INSERM U981, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France., Institute of Cancer and Genomic Services, University of Birmingham, and Cancer Centre, Queen Elizabeth Hospital, Birmingham, UK., CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK., Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain., Hospital Universitario HM Sanchinarro, Madrid, Spain., Cannizzaro Hospital, Catania, Italy., Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Meldola, Italy., Medical Oncology Unit, AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italy., Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece., Institut Catala d'Oncologia, IDIBELL, University of Barcelona, Barcelona, Spain., Hospital Universitario Virgen del Rocio, Seville, Spain., Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew's Hospital, London, UK., University Hospital Centre 'Zagreb', Zagreb, Croatia., Department of Urology, University Hospital Ulm, Ulm, Germany., National Institute of Oncology, Budapest, Hungary., Calvary Mater Newcastle, Waratah, Australia., F. Hoffmann-La Roche, Basel, Switzerland., Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany.