Yohann Loriot1, Cora N Sternberg2, Daniel Castellano3, Sjoukje F Oosting4, Herlinde Dumez5, Robert Huddart6, Karina Vianna7, Teresa Alonso Gordoa8, Iwona Skoneczna9, Andre P Fay10, Franco Nolè11, Francesco Massari12, Birute Brasiuniene13, Pablo Maroto14, Simon Fear15, Flavia Di Nucci16, Sabine de Ducla17, Ernest Choy18. 1. Department of Cancer Medicine and INSERM U981, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France. Electronic address: yohann.loriot@gustaveroussy.fr. 2. San Camillo and Forlanini Hospitals, Rome, Italy; Weill Cornell Medicine, New York, NY, USA. Electronic address: cns9006@med.cornell.edu. 3. Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain. Electronic address: cdanicas@hotmail.com. 4. Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: s.oosting@umcg.nl. 5. Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. Electronic address: herlinde.dumez@uzleuven.be. 6. Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, UK. Electronic address: Robert.Huddart@icr.ac.uk. 7. Centro Integrado de Oncologia de Curitiba (CIONC), Curitiba, Brazil. Electronic address: kcmvianna@yahoo.com.br. 8. Medical Oncology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain. Electronic address: teressalonso25@gmail.com. 9. Szpital św. Elżbiety, Mokotowskie Centrum Medyczne, Warsaw, Poland. Electronic address: iwona.skoneczna@szpitalse.pl. 10. Oncoclínicas Group, PUCRS School of Medicine, Porto Alegre, Brazil. Electronic address: andrepfay@gmail.com. 11. Medical Oncology Division of Urogenital and Head & Neck Tumours, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: franco.nole@ieo.it. 12. Division of Oncology, Sant'Orsola-Malpighi Hospital, Bologna, Italy. Electronic address: francesco.massari@aosp.bo.it. 13. National Cancer Institute, Vilnius, Lithuania. Electronic address: birute.brasiuniene@nvi.lt. 14. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: jmaroto@santpau.cat. 15. F Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: simon.fear@roche.com. 16. Genentech, Inc., South San Francisco, CA, USA. Electronic address: di-nucci.flavia@gene.com. 17. F Hoffmann-La Roche Ltd, Basel, Switzerland. Electronic address: sabine.de_ducla@roche.com. 18. CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. Electronic address: choyeh@cardiff.ac.uk.
Abstract
AIM: Patients with pre-existing autoimmune disease (AID) are typically excluded from clinical trials of immune checkpoint inhibitors, and there are limited data on outcomes in this population. The single-arm international SAUL study of atezolizumab enrolled a broader 'real-world' patient population. We present outcomes in patients with a history of AID. METHODS: Patients with locally advanced/metastatic urinary tract carcinoma received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary end-point was safety. Overall survival (OS) was a secondary end-point. Subgroup analyses of AID patients were prespecified. RESULTS: Thirty-five of 997 treated patients had AID at baseline, most commonly psoriasis (n = 15). Compared with non-AID patients, AID patients experienced numerically more adverse events (AEs) of special interest (46% versus 30%; grade ≥3 14% versus 6%) and treatment-related grade 3/4 AEs (26% versus 12%), but without relevant increases in treatment-related deaths (0% versus 1%) or AEs necessitating treatment discontinuation (9% versus 6%). Pre-existing AID worsened in four patients (11%; two flares in two patients); three of the six flares resolved, one was resolving, and two were unresolved. Efficacy was similar in AID and non-AID patients (median OS, 8.2 versus 8.8 months, respectively; median progression-free survival, 4.4 versus 2.2 months; disease control rate, 51% versus 39%). CONCLUSIONS: In 35 atezolizumab-treated patients with pre-existing AID, incidences of special- interest and treatment-related AEs appeared acceptable. AEs were manageable, rarely requiring atezolizumab discontinuation. Treating these patients requires caution, but pre-existing AID does not preclude atezolizumab therapy. TRIAL REGISTRATION: NCT02928406.
AIM: Patients with pre-existing autoimmune disease (AID) are typically excluded from clinical trials of immune checkpoint inhibitors, and there are limited data on outcomes in this population. The single-arm international SAUL study of atezolizumab enrolled a broader 'real-world' patient population. We present outcomes in patients with a history of AID. METHODS:Patients with locally advanced/metastatic urinary tract carcinoma received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary end-point was safety. Overall survival (OS) was a secondary end-point. Subgroup analyses of AID patients were prespecified. RESULTS: Thirty-five of 997 treated patients had AID at baseline, most commonly psoriasis (n = 15). Compared with non-AID patients, AID patients experienced numerically more adverse events (AEs) of special interest (46% versus 30%; grade ≥3 14% versus 6%) and treatment-related grade 3/4 AEs (26% versus 12%), but without relevant increases in treatment-related deaths (0% versus 1%) or AEs necessitating treatment discontinuation (9% versus 6%). Pre-existing AID worsened in four patients (11%; two flares in two patients); three of the six flares resolved, one was resolving, and two were unresolved. Efficacy was similar in AID and non-AID patients (median OS, 8.2 versus 8.8 months, respectively; median progression-free survival, 4.4 versus 2.2 months; disease control rate, 51% versus 39%). CONCLUSIONS: In 35 atezolizumab-treated patients with pre-existing AID, incidences of special- interest and treatment-related AEs appeared acceptable. AEs were manageable, rarely requiring atezolizumab discontinuation. Treating these patients requires caution, but pre-existing AID does not preclude atezolizumab therapy. TRIAL REGISTRATION: NCT02928406.