SYSTEMATIC REVIEW OF ADVERSE EVENTS ASSOCIATED WITH THE IMMUNOTHERAPY CHECKPOINT INHIBITOR DRUG CLASS

OBJECTIVES

The checkpoint inhibitor drug class exerts its effect by up-regulating the immune system to attack cancer cells. There are currently six US FDA-approved checkpoint inhibitors for oncologic treatment: ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab and durvalumab. We sought to systematically describe the incidence and timing of adverse events associated with the checkpoint inhibitor drug class.

METHODS

We searched Medline, Embase, Cochrane Library, and the CINAHL databases for articles published between January 2011 and September 2018. The search was restricted to include studies of US adults (≥18 years old) with the six approved checkpoint inhibitors. Only full text randomized, prospective, or retrospective studies were included.

RESULTS

Of the 2,230 unique articles identified, 248 articles were identified for full text review and 38 final articles were included in this review (N=8,156 patients). The most commonly studied drugs were pembrolizumab (N=17), nivolumab (N=9), and ipilimumab (N=5). The most commonly studied tumor types were melanoma (N=11), non-small cell lung cancer (N=7), and urothelial carcinoma (N=5). The most commonly reported serious treatment-related adverse events of grade 3 or higher were fatigue (N=149, 1.8%), diarrhea (N=111, 1.4%), ALT increase (N=64, 0.8%), AST increase (N=59, 0.7%), and rash (N=49, 0.6%). The most commonly reported serious immune-related adverse events of grade 3 or higher were diarrhea (N=112, 1.4%), colitis (N=80, 1.0%), hepatotoxicity (N=61, 0.7%), pneumonitis (N=57, 0.7%), and hypophysitis (N=39, 0.5%). The average median time to onset for serious treatment-related adverse events was 20.31 weeks and for serious immune-related adverse events the median time to onset was 7.16 weeks.

CONCLUSIONS

This review attempts to describe the adverse events associated with this drug class but also reveals the gaps in literature that are currently present. More research is required to better characterize the adverse events of the newer checkpoint inhibitors in clinical practice.