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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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. Patient summary: 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.

Original languageEnglish
JournalEuropean Urology
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Urinary Tract
Carcinoma
Safety
Confidence Intervals
Therapeutics
Survival
Autoimmune Diseases
Disease-Free Survival
MPDL3280A
Urologic Neoplasms
Population
Antibodies, Monoclonal, Humanized
Asthenia
Colitis
Life Expectancy
Platinum
Fatigue
Adrenal Cortex Hormones
Survival Rate
Central Nervous System

Keywords

  • Atezolizumab
  • Autoimmune disease
  • Central nervous system metastases
  • Immunotherapy
  • Nonurothelial carcinoma
  • PD-L1
  • Real world
  • Steroid
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

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; Merseburger, Axel S.

In: European Urology, 01.01.2019.

Research output: Contribution to journalArticle

Sternberg, CN, Loriot, Y, James, N, Choy, E, Castellano, D, Lopez-Rios, F, Banna, GL, De Giorgi, U, Masini, C, Bamias, A, Garcia del Muro, X, Duran, I, Powles, T, Gamulin, M, Zengerling, F, Geczi, L, Gedye, C, de Ducla, S, Fear, S & Merseburger, AS 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. https://doi.org/10.1016/j.eururo.2019.03.015
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 ; Merseburger, Axel S. / 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. In: European Urology. 2019.
@article{633474022bef40038964aaf2861051cc,
title = "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",
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. Patient summary: 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.",
keywords = "Atezolizumab, Autoimmune disease, Central nervous system metastases, Immunotherapy, Nonurothelial carcinoma, PD-L1, Real world, Steroid, Urothelial carcinoma",
author = "Sternberg, {Cora N.} and Yohann Loriot and Nicholas James and Ernest Choy and Daniel Castellano and Fernando Lopez-Rios and Banna, {Giuseppe L.} and {De Giorgi}, Ugo and Cristina Masini and Aristotelis Bamias and {Garcia del Muro}, Xavier and Ignacio Duran and Thomas Powles and Marija Gamulin and Friedemann Zengerling and Lajos Geczi and Craig Gedye and {de Ducla}, Sabine and Simon Fear and Merseburger, {Axel S.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.eururo.2019.03.015",
language = "English",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - 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

AU - Sternberg, Cora N.

AU - Loriot, Yohann

AU - James, Nicholas

AU - Choy, Ernest

AU - Castellano, Daniel

AU - Lopez-Rios, Fernando

AU - Banna, Giuseppe L.

AU - De Giorgi, Ugo

AU - Masini, Cristina

AU - Bamias, Aristotelis

AU - Garcia del Muro, Xavier

AU - Duran, Ignacio

AU - Powles, Thomas

AU - Gamulin, Marija

AU - Zengerling, Friedemann

AU - Geczi, Lajos

AU - Gedye, Craig

AU - de Ducla, Sabine

AU - Fear, Simon

AU - Merseburger, Axel S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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. Patient summary: 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.

AB - 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. Patient summary: 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.

KW - Atezolizumab

KW - Autoimmune disease

KW - Central nervous system metastases

KW - Immunotherapy

KW - Nonurothelial carcinoma

KW - PD-L1

KW - Real world

KW - Steroid

KW - Urothelial carcinoma

UR - http://www.scopus.com/inward/record.url?scp=85063135819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063135819&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2019.03.015

DO - 10.1016/j.eururo.2019.03.015

M3 - Article

JO - European Urology

JF - European Urology

SN - 0302-2838

ER -