O Abdel-Rahman1, D Helbling2, J Schmidt3, U Petrausch4, A Giryes2, A Mehrabi5, O Schöb3, M Mannhart6, A Zidan7, H Oweira8. 1. Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; OncoCentrum Zurich, Gastrointestinal Tumor Center Zurich (GITZ), Zurich, Switzerland. Electronic address: omar.abdelrhman@med.asu.edu.eg. 2. OncoCentrum Zurich, Gastrointestinal Tumor Center Zurich (GITZ), Zurich, Switzerland. 3. Surgical Center Zurich - Hirslanden Hospital Zurich, Switzerland. 4. OncoCentrum Zurich, Swiss Tumor Immunology Institute (SwissTII), Zurich, Switzerland. 5. Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany. 6. Department of Oncology, Center of Zug, Switzerland. 7. Department of HPB and Liver Transplantation, Rajhy Liver Hospital, Assiut University, Assiut, Egypt. 8. Surgical Center Zurich - Hirslanden Hospital Zurich, Switzerland; Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
Abstract
AIMS: Fatigue is one of the most prominent side-effects of immune checkpoint inhibition. Therefore, we assessed the risk of fatigue associated with inhibitors of the immune checkpoints. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, nivolumab, pembrolizumab and tremelimumab. The authors extracted relevant information on participants(') characteristics, all-grade and high-grade fatigue and information on the methodology of the studies. RESULTS: In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade fatigue for CTLA-4 inhibitors was 1.23 (95% confidence interval 1.07, 1.41; P = 0.003) and for high-grade fatigue was 1.72 (95% confidence interval 1.26, 2.33; P = 0.0005). Moreover, the odds ratio for all-grade fatigue for PD-1 inhibitors was 0.72 (95% confidence interval 0.62, 0.84; P < 0.0001) and for high-grade fatigue was 0.36 (95% confidence interval 0.23, 0.56; P < 0.00001). CONCLUSIONS: The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade fatigue compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade fatigue compared with control regimens.
AIMS: Fatigue is one of the most prominent side-effects of immune checkpoint inhibition. Therefore, we assessed the risk of fatigue associated with inhibitors of the immune checkpoints. MATERIALS AND METHODS: We examined data from the Medline and Google Scholar databases. We also examined original studies and review articles for cross-references. Eligible studies included randomised phase II and phase III trials of patients with cancer treated with ipilimumab, nivolumab, pembrolizumab and tremelimumab. The authors extracted relevant information on participants(') characteristics, all-grade and high-grade fatigue and information on the methodology of the studies. RESULTS: In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade fatigue for CTLA-4 inhibitors was 1.23 (95% confidence interval 1.07, 1.41; P = 0.003) and for high-grade fatigue was 1.72 (95% confidence interval 1.26, 2.33; P = 0.0005). Moreover, the odds ratio for all-grade fatigue for PD-1 inhibitors was 0.72 (95% confidence interval 0.62, 0.84; P < 0.0001) and for high-grade fatigue was 0.36 (95% confidence interval 0.23, 0.56; P < 0.00001). CONCLUSIONS: The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade fatigue compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade fatigue compared with control regimens.
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