Multiorgan Immune-Related Adverse Events During Treatment With Atezolizumab

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  • 1 Department of Clinical Pharmacology, College of Medicine and Public Health, and
  • 2 Department of Medical Oncology, Flinders Centre for Innovation in Cancer, Flinders Medical Centre/Flinders University, Bedford Park, South Australia, Australia.
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Background: Immune-related adverse events (irAEs) are known to occur in patients with cancer who are treated with immune checkpoint inhibitors. However, limited literature exists on the incidence, time of onset, and risk factors for irAEs, particularly those affecting multiple organs, associated with anti–PD-L1 inhibitors. Methods: A post hoc pooled analysis was conducted using individual patient data from atezolizumab monotherapy arms of 4 non–small cell lung cancer clinical trials. Incidence, clinical patterns, outcomes, and risk factors were investigated of selected organ-specific and multiorgan irAEs during treatment using the anti–PD-L1 inhibitor atezolizumab. Results: From a total of 1,548 patients, 730 irAE episodes were reported in 424 patients (27%). Skin irAEs were the most common (42%), followed by laboratory abnormalities (27%) and endocrine (11.6%), neurologic (7.6%), and pulmonary (6.2%) irAEs. A total of 84 patients (5.4%) had multiorgan irAEs, 70 had 2, 13 had 3, and 1 had 4 different organs affected. “Skin plus” or “laboratory plus” were the most common irAE multiorgan clusters. Patients with multiorgan irAEs were more likely to be white and have a good performance status, a lower baseline neutrophil-lymphocyte ratio, and a good or intermediate lung immune prognostic index score. Multiorgan irAEs were also associated with improved overall survival (hazard ratio, 0.47; 95% CI, 0.28–0.78; P<.0001) but not with progression-free survival (hazard ratio, 0.92; 95% CI, 0.62–1.35; P=.74) compared with the cohort with no irAEs. Conclusions: Multiorgan irAEs occurred in 5.4% of patients treated with atezolizumab in non–small cell lung cancer trials. Future trials should consider routine reporting of data on multiorgan toxicities in addition to organ-specific toxicities.

Submitted January 25, 2020; accepted for publication March 27, 2020.

Author contributions: Study concept and design: Kichenadasse, Hopkins, Sorich. Funding: Hopkins, Sorich. Data acquisition: Hopkins, Sorich. Data analysis and interpretation: Miners, Mangoni, Rowland, Hopkins, Sorich. Statistical analysis: Kichenadasse. Technical support: Miners, Rowland, Hopkins. Technical/Material support: Mangoni. Supervision: Miners, Mangoni, Rowland, Hopkins, Sorich. Manuscript preparation: All authors. Critical revision for intellectual content: All authors.

Disclosures: Dr. Rowland has disclosed that he has received grant/research support from Pfizer. Dr. Sorich has disclosed that he has received grant/research support from Pfizer. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by a research grant by Cancer Council South Australia (1159924 and 1127220 to Dr. Sorich) and the National Breast Cancer Foundation (grant PF-17-007 to Dr. Hopkins).

Disclaimer: Individual-participant data used were accessed via https://www.clinicalstudydatarequest.com, according to Roche’s policy and process for clinical study data-sharing.

Correspondence: Ganessan Kichenadasse, MBBS, FRACP, Department of Medical Oncology, Flinders Centre for Innovation in Cancer, Flinders Medical Centre/Flinders University, Bedford Park, South Australia 5042, Australia. Email: ganessan.kichenadasse@flinders.edu.au

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