Safety and efficacy of atezolizumab in patients with autoimmune disease: Subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma.

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.
Competing Interests: Conflict of interest statement Y.L. reports a grant and non-financial support from Roche for the SAUL study and funding of editorial support, a grant from Celsius, grants and personal fees from Sanofi, Janssen and MSD and personal fees from Astellas, AstraZeneca, Roche, BMS, Seattle Genetics and Pfizer. C.N.S. reports consultancy for Pfizer, MSD, Merck, AstraZeneca, Astellas, Sanofi-Genzyme, Roche/Genentech and Incyte. D.C. reports research funding to his institution from Janssen Oncology; adviser/consultancy to Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, Bristol-Myers Squibb, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre and Boehringer Ingelheim; travel/accommodation/expenses from Pfizer, Roche, Bristol-Myers Squibb and AstraZeneca Spain. S.F.O. reports research grants to institution from Celldex and Novartis. H.D. reports travel/accommodation/expenses from Astellas, Roche, Pfizer, Bayer, AstraZeneca, Novartis, Sanofi, Ipsen, MSD and Janssen-Cilag. R.H. reports grants and personal fees from MSD; grants, personal fees and non-financial support from Roche; personal fees and non-financial support from Nektar and Janssen; personal fees from Bayer, BMS and NICE; partnership in Cancer Centre London. K.V. reports adviser/consultancy to Lilly, Novartis, Bayer and Pfizer; speaker bureau/expert testimony for Roche, AstraZeneca, Lilly and BMS. T.A.G. reports adviser/consultancy to BMS, MSD, Roche, Astellas, Ipsen, Sanofi-Genzyme, Eisai, Bayer; speaker bureau/expert testimony for Pfizer, Ipsen, Janssen and Astellas; research grant/funding to institution from Roche, Ipsen and Pfizer; travel/accommodation/expenses from Pfizer, Sanofi-Genzyme and Ipsen. I.S. reports grants, personal fees and non-financial support from Roche. A.P.F. reports research grants from Roche, personal fees from BMS, Roche, Novartis, Janssen, Astellas, Merck and AstraZeneca and non-financial support from BMS, Roche, Janssen, Astellas, Merck, Ipsen and AstraZeneca. B.B. reports personal fees for adviser/consultant roles from Roche, Novartis, Pfizer, Eli Lilly, Swixx BioPharma and Ipsen, travel/accommodation expenses from AstraZeneca, Janssen, Pfizer, Bausch Health and Ipsen and non-financial support for adviser/consultant roles from GSK. P.M. reports adviser/consultancy to Pfizer, Novartis, Janssen, Roche, Sanofi, Bayer and BMS; research grant/funding to institution from Roche. S.F. works for Roche (under contract via Hayes Schweiz AG). F.Di.N. reports employment with Roche/Genentech; share/stockholder of Roche/Genentech. S.de.D. reports employment with F Hoffmann-La Roche Ltd; shareholder of F Hoffmann-La Roche Ltd. E.C. reports personal fees from Chugai Pharma, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Gilead, AbbVie, R-Pharm, SynAct Pharma and ObsEva and research grants from Chugai Pharma, Novartis, Pfizer, Roche, Sanofi, UCB, Biogen and Bio-Cancer. F.N. and F.M. declare no conflicts of interest.
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