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Clin Oncol (R Coll Radiol). 2017 Apr;29(4):218-230. doi: 10.1016/j.clon.2016.11.007. Epub 2016 Nov 25.

Treatment-related Death in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

Author information

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
Surgical Center Zurich, Hirslanden Hospital, Zurich, Switzerland; Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.

Abstract

AIMS:

We carried out a meta-analysis to determine the risk of treatment-related death associated with immune checkpoint inhibitor use in cancer patients.

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, pembrolizumab; nivolumab; tremelimumab and atezolizumab. The authors extracted relevant information on participants, characteristics, treatment-related death and information on the methodology of the studies.

RESULTS:

After exclusion of ineligible records, 18 clinical trials were included in the analysis. The odds ratio for treatment-related death for CTLA-4 inhibitors (ipilimumab and tremelimumab) was 1.80 (95% confidence interval 1.25, 2.59; P=0.002) and for PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) was 0.63 (95% confidence interval 0.31, 1.30; P=0.22). Treated cancer seems to have no effect on the risk of treatment-related death.

CONCLUSIONS:

Analysis of our data showed that CTLA-4 inhibitors (ipilimumab and tremelimumab) in a higher dose (10 mg/kg) seem to be associated with a higher risk of treatment-related death compared with control regimens, whereas PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and atezolizumab) do not cause the same risk. Clinicians have to be fully aware of these differential risks and council their patients appropriately.

KEYWORDS:

Atezolizumab; ipilimumab; nivolumab; pembrolizumab; treatment-related death; tremelimumab

PMID:
27894673
DOI:
10.1016/j.clon.2016.11.007
[Indexed for MEDLINE]

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