Insomnia in patients treated with checkpoint inhibitors for cancer: A meta-analysis

Igor Kiss; Matyas Kuhn; Kristian Hrusak; Benjamin Buchler; Ludmila Boublikova; Tomas Buchler

doi:10.3389/fonc.2022.946307

Insomnia in patients treated with checkpoint inhibitors for cancer: A meta-analysis

Front Oncol. 2022 Aug 2:12:946307. doi: 10.3389/fonc.2022.946307. eCollection 2022.

Authors

Igor Kiss¹, Matyas Kuhn², Kristian Hrusak³, Benjamin Buchler³, Ludmila Boublikova³, Tomas Buchler³

Affiliations

¹ Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czechia.
² Institute of Biostatistics and Analyses, Masaryk University, Brno, Czechia.
³ Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czechia.

Abstract

Purpose: Insomnia in cancer patients is a common symptom contributing to poor quality of life and poor functioning. Sleep disturbances have been associated with inflammatory activity, and systemic cancer therapies chemotherapy, hormonal therapy, and immunotherapy may cause insomnia. We have carried out a meta-analysis to estimate the occurrence of insomnia in patients with solid cancer treated with immunotherapy using checkpoint inhibitors (CPI).

Methods: PubMed and ClinicalTrials.gov were searched for phase 3 studies in solid tumours where treatment included a checkpoint inhibitor in the experimental arm. Data on the incidence of insomnia were acquired from the adverse events tables available from clinicaltrials.gov and/or from the full texts. Random effect logistic model was used to compare pooled data. Heterogeneity between studies was assessed using Cochrane Q statistics and I² statistics.

Results: A total of 54 studies (including six three-arm studies) involving 37,352 patients were included in the analysis. Insomnia was reported in 8.3% of subjects (95% confidence interval [CI] 8.0%-8.7%) treated with immunotherapy. Insomnia was significantly more common in patients receiving immunotherapy compared to those enrolled in study arms with inactive treatment (odds ratio [OR] 1.49, 95% CI 1.13-1.96). The odds for insomnia were similar between the arms for studies comparing CPI versus chemotherapy and CPI versus non-immunologic targeted therapies (OR 1.07, 95% CI 0.94-1.22 and OR 1.40, 95% CI 0.90-2.18, respectively). The OR for insomnia was higher for cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor inhibitors compared to the inhibitors of programmed death-1 (PD-1) receptor (OR 1.36, 95% CI 1.06 - 1.74).

Conclusion: Cancer immunotherapy using CPI is associated with insomnia but the odds of developing the symptom are not greater with immunotherapy than with other systemic modalities including chemotherapy and non-immunologic targeted therapies.

Keywords: cancer; checkpoint inhibitors; immunotherapy; insomnia; systematic analysis.

Publication types

Systematic Review