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

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.

• Authors: Yohann Loriot, Cora N Sternberg, Daniel Castellano, Sjoukje F Oosting, Herlinde Dumez, Robert Huddart, Karina Vianna, Teresa Alonso Gordoa, Iwona Skoneczna, Andre P Fay, Franco Nolè, Francesco Massari, Birute Brasiuniene, Pablo Maroto, Simon Fear, Flavia Di Nucci, Sabine de Ducla, Ernest Choy
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 138 Pg. 202-211 (10 2020) ISSN: 1879-0852 [Electronic] England
• PMID: 32905959 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents, Immunological
• Immune Checkpoint Inhibitors
• atezolizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Antineoplastic Agents, Immunological (adverse effects, therapeutic use)
• Autoimmune Diseases (diagnosis, immunology, mortality)
• Autoimmunity
• Carcinoma (drug therapy, immunology, mortality, secondary)
• Clinical Decision-Making
• Disease Progression
• Female
• Humans
• Immune Checkpoint Inhibitors (adverse effects, therapeutic use)
• Male
• Middle Aged
• Progression-Free Survival
• Prospective Studies
• Risk Factors
• Time Factors
• Urologic Neoplasms (drug therapy, immunology, mortality, pathology)