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Ann Oncol. 2015 Sep;26(9):1824-9. doi: 10.1093/annonc/mdv182. Epub 2015 Apr 17.

A systematic review of immune-related adverse event reporting in clinical trials of immune checkpoint inhibitors.

Author information

1
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto Department of Medicine, University of Toronto, Toronto, Canada.
2
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre-University Health Network, Toronto Department of Medicine, University of Toronto, Toronto, Canada aaron.hansen@uhn.ca.

Abstract

BACKGROUND:

There are limited data about the quality of immune-related adverse event (irAE) reporting in immune checkpoint inhibitor (ICI) clinical trial publications.

METHODS:

A systematic search of citations from Medline, EMBASE and Cochrane databases identified prospective clinical trials involving ICIs in advanced solid tumors from 2003 to 2013. A 21-point quality score (QS) was adapted from the CONSORT harms extension statement. Linear regression was used to identify factors associated with quality reporting.

RESULTS:

After a review of 2628 articles, 50 trial reports were included, with ICIs as either monotherapy (54%) or part of a combination regimen (46%). The mean QS was 11.21 points (range 3.50-17.50 points). The median grade 3/4 AE rate reported was 21% (range 0%-66%) and 29/50 (58%) trials concluded that irAEs were tolerable. Multivariate regression analysis revealed that year of publication (within last 5 years, P = 0.01) and journal impact factor >15 (P = 0.004) were associated with higher QS. Complete reporting of specific characteristics of irAEs including onset, management and reversibility were reported by 14%, 8% and 6% of studies, respectively. The incidence of grade 3/4 adverse events was higher for inhibitors against CTLA-4 compared with other immune checkpoints (P < 0.001).

CONCLUSIONS:

The reporting of irAEs is suboptimal. A standardized reporting method of irAEs that accounts for tolerability, management and reversibility is needed and would enable a more precise evaluation of the therapeutic risk benefit ratio of ICIs.

KEYWORDS:

adverse event; immune checkpoint inhibitors; quality control; systematic review

PMID:
25888611
DOI:
10.1093/annonc/mdv182
[Indexed for MEDLINE]

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