Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors: A Scoping Review Protocol

Background: Immune checkpoint inhibitors (ICIs) have changed the cancer treatment by enhancing the immune system's ability to target tumors. ICIs include ipilimumab (CTLA-4), pembrolizumab, nivolumab, cemiplimab (PD-1), atezolizumab and durvalumab (PD-L1) which have improved survival in cancers like melanoma and non-small cell lung cancer (NSCLC). However, their use is often associated with immune-related adverse events (irAEs), complicating treatment and quality of life. The heterogeneity of reported irAEs across different studies complicates efforts to establish standardized definitions and treatment guidelines. As such, there is a need in medical literature to identify trends, gaps in knowledge, and areas for future research.Objectives: This scoping review aims to assess irAEs associated with ICIs in lung cancer, melanoma, breast cancer and colon cancer, evaluating their incidence, clinical characteristics, management strategies, and outcomes.Methods: We assessed first the Medicine Agency (MA) data sources for labeled irAEs associated with ICIs and then we conducted a comprehensive literature review according to PRISMA guidelines. We extracted the information from the Summary of Product Characteristics (SPC) of each ICI approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to highlight similarities and differences between the two. Then we retrieved from PubMed observational studies and target trail emulation studies performed using data collected in administrative healthcare databases (AHDs) and in spontaneous reporting systems (SRSs), by including only those focused on irAEs associated with ICIs in the cancers of interest.Conclusions: We highlighted missing information regarding time to onset, duration of irAEs, comorbidities, concomitant therapies, therapy dechallenge and rechallenge. Finalizing this scoping review will provide a comprehensive safety profile from SPCs to real-world about irAEs associated with ICIs and will emphasize knowledge gaps that will be investigated in ad hoc studies.