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Differences in immune-related toxicity between PD-1 and PD-L1 inhibitors: a retrospective cohort study in patients with advanced cancer
Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, 751 85, Uppsala, Sweden.
Thoracic Oncology Center, Theme Cancer, Karolinska University Hospital, 171 76, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, 171 77, Stockholm, Sweden.
Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, 751 85, Uppsala, Sweden.
Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University Hospital, 751 85, Uppsala, Sweden.
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2024 (English)In: Cancer Immunology and Immunotherapy, ISSN 0340-7004, E-ISSN 1432-0851, Vol. 74, no 1, article id 14Article in journal (Refereed) Published
Abstract [en]

Immunotherapy with PD-1 or PD-L1 inhibitors has become an essential treatment strategy for a growing number of malignancies. These treatments have a risk for immune-related adverse events (IRAEs). Pooled analyses based on clinical trials show a favorable toxicity profile for treatment with PD-L1 compared to PD-1 inhibitors. This study aimed to investigate differences in IRAEs between patients with advanced solid malignances treated with PD-L1 and PD-1 inhibitors in a real-world setting. We conducted a retrospective cohort study at four Swedish Regions. Patients (n = 605) treated for advanced cancer with a PD-L1 or PD-1 inhibitor in monotherapy between June 2016 and August 2022 were included. Non-small cell lung cancer (NSCLC) was the most common malignant disease (n = 251; 41.5%), followed by malignant melanoma (n = 173; 28.6%), renal cell carcinoma (n = 71; 11.7%) and urothelial carcinoma (n = 35; 5.8%). Among patients receiving PD-L1 inhibitors, NSCLC (94.4%) was the predominant malignancy, whereas for those treated with PD-1 inhibitor, malignant melanoma constituted the most prevalent malignancy (34.5%). Discontinuation of treatment due to IRAEs overall and IRAEs grade ≥ 2 were significantly less common in patients treated with PD-L1 compared to PD-1 inhibitors [Odds Ratio (OR): 0.38 (95% Confidence Interval (CI) 0.16-0.88) and OR: 0.63 (95% CI 0.35-0.98) respectively]. Any grade IRAE, IRAE grade ≥ 3 and multiple IRAEs were numerically more frequent in patients treated with PD-1 inhibitors.In conclusion, our study of patients with advanced solid malignancies in a real-world setting supports the results from clinical trials demonstrating a favorable toxicity profile for PD-L1 inhibitors versus PD-1 inhibitors.

Place, publisher, year, edition, pages
Springer, 2024. Vol. 74, no 1, article id 14
Keywords [en]
Advanced cancer, Cohort study, Immune-related adverse events, PD-1 inhibitors, PD-L1 inhibitors
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-117354DOI: 10.1007/s00262-024-03869-1ISI: 001352314200002PubMedID: 39508883Scopus ID: 2-s2.0-85209155381OAI: oai:DiVA.org:oru-117354DiVA, id: diva2:1913474
Funder
Örebro UniversityStiftelsen Onkologiska Klinikens i Uppsala ForskningsfondRegion UppsalaThe Cancer Society in Stockholm, 009618Available from: 2024-11-15 Created: 2024-11-15 Last updated: 2024-11-26Bibliographically approved

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Valachis, Antonios

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