Adverse events reporting in phase 3 oncology clinical trials of checkpoint inhibitors: A systematic review

Abstract

Introduction: This study aimed at exploring adverse events (AEs) reporting in cancer trials involving immune checkpoint inhibitors (ICIs).

Method: A systematic review on how ICIs phase 3 trials follow TRIO and 2004 CONSORT harms extension recommendations referring to toxicity was performed by two independent reviewers.

Results: Among 46 trials included, 74 % did not present separately grade 3 and grade 4 AEs. Timing of onset and duration were reported in 30 % and 28 %, respectively. AEs occurring in <10 % of patients were only reported in 35 % of studies. Patient-related outcomes (PROs) were analyzed in only 17 % of reports. Eight articles qualified the toxicity profile as "manageable", "tolerable", "well tolerated" or "favorable" despite reporting a rate of grade 3-4 greater than 33 %.

Conclusion: Reporting toxicity results is crucial. However, toxicity reporting is highly incomplete in clinical trials. Guidelines, new metrics and incorporation of PROs are needed for a comprehensive knowledge of toxicity profile.

Keywords: Adverse event; Immune checkpoint inhibitors; Immune toxicity; Quality reporting; Systematic review.