Cora N Sternberg1, Yohann Loriot2, Nicholas James3, Ernest Choy4, Daniel Castellano5, Fernando Lopez-Rios6, Giuseppe L Banna7, Ugo De Giorgi8, Cristina Masini9, Aristotelis Bamias10, Xavier Garcia Del Muro11, Ignacio Duran12, Thomas Powles13, Marija Gamulin14, Friedemann Zengerling15, Lajos Geczi16, Craig Gedye17, Sabine de Ducla18, Simon Fear18, Axel S Merseburger19. 1. San Camillo and Forlanini Hospitals, Rome, Italy. Electronic address: cns9006@med.cornell.edu. 2. Department of Cancer Medicine and INSERM U981, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France. 3. Institute of Cancer and Genomic Services, University of Birmingham, and Cancer Centre, Queen Elizabeth Hospital, Birmingham, UK. 4. CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. 5. Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain. 6. Hospital Universitario HM Sanchinarro, Madrid, Spain. 7. Cannizzaro Hospital, Catania, Italy. 8. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Meldola, Italy. 9. Medical Oncology Unit, AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italy. 10. Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece. 11. Institut Catala d'Oncologia, IDIBELL, University of Barcelona, Barcelona, Spain. 12. Hospital Universitario Virgen del Rocio, Seville, Spain. 13. Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew's Hospital, London, UK. 14. University Hospital Centre 'Zagreb', Zagreb, Croatia. 15. Department of Urology, University Hospital Ulm, Ulm, Germany. 16. National Institute of Oncology, Budapest, Hungary. 17. Calvary Mater Newcastle, Waratah, Australia. 18. F. Hoffmann-La Roche, Basel, Switzerland. 19. Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany.
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 12.7mo), 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 (Clinicaltrials.gov: NCT02928406). INTERVENTION: Atezolizumab 1200mg every 3wk 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 2.8mo (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%). 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.
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 12.7mo), 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 (Clinicaltrials.gov: NCT02928406). INTERVENTION: Atezolizumab 1200mg every 3wk 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 2.8mo (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%). 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.
Authors: Alexander Tamalunas; Gerald B Schulz; Severin Rodler; Maria Apfelbeck; Christian G Stief; Jozefina Casuscelli Journal: Urologe A Date: 2021-02 Impact factor: 0.639
Authors: Jens Bedke; Axel S Merseburger; Yohann Loriot; Daniel Castellano; Ernest Choy; Ignacio Duran; Jonathan E Rosenberg; Daniel P Petrylak; Robert Dreicer; Jose L Perez-Gracia; Jean H Hoffman-Censits; Michiel S Van Der Heijden; Julie Pavlova; Lars Thiebach; Sabine de Ducla; Simon Fear; Thomas Powles; Cora N Sternberg Journal: Eur Urol Focus Date: 2020-11-06
Authors: Ali Raza Khaki; Ang Li; Leonidas N Diamantopoulos; Mehmet A Bilen; Victor Santos; John Esther; Rafael Morales-Barrera; Michael Devitt; Ariel Nelson; Christopher J Hoimes; Evan Shreck; Hussein Assi; Benjamin A Gartrell; Alex Sankin; Alejo Rodriguez-Vida; Mark Lythgoe; David J Pinato; Alexandra Drakaki; Monika Joshi; Pedro Isaacsson Velho; Noah Hahn; Sandy Liu; Lucia Alonso Buznego; Ignacio Duran; Marcus Moses; Jayanshu Jain; Jure Murgic; Praneeth Baratam; Pedro Barata; Abhishek Tripathi; Yousef Zakharia; Matthew D Galsky; Guru Sonpavde; Evan Y Yu; Veena Shankaran; Gary H Lyman; Petros Grivas Journal: Cancer Date: 2019-12-12 Impact factor: 6.921