Uncovering Knowledge Gaps in the Safety Profile of Antiangiogenic Drugs in Cancer Patients: Insights from Spontaneous Reporting Systems Studies

Global repositories of postmarketing safety reports improve understanding of real-life drug toxicities, often not observed in clinical trials. The aim of this scoping review was to map the evidence from spontaneous reporting systems studies (SRSs) of antiangiogenic drugs (AADs) in cancer patients and highlight if the found disproportionality signals of adverse events (AEs) were validated and thus mentioned in the respective Summary of product Characteristics (SmPC). This scoping review was conducted according to PRISMA guidelines for scoping reviews. A knowledge gap on the safety of AADs was found: firstly, several cardiovascular AEs were not mentioned in the SmPCs and no pharmacovigilance studies were conducted despite the well-known safety concerns about these drugs on the cardiovascular system. Second, a disproportionality signal (not validated through causality assessment) of pericardial disease was found in the literature for axitinib with no mention in SmPC of the drug. Despite the exclusion of pharmacoepidemiological studies, we believe that this scoping review, which focuses on an entire class of drugs, could be considered as a novel approach to highlight possible safety concerns of drugs and as a guide for the conduction of a target postmarketing surveillance on AADs.

Automated summary

Global repositories of postmarketing safety reports provide important insights into real-life drug toxicities beyond clinical trials. This scoping review focuses on spontaneous reporting systems studies (SRSs) of antiangiogenic drugs (AADs) in cancer patients and examines whether adverse events (AEs) identified in these studies were validated and mentioned in the respective Summary of Product Characteristics (SmPCs). The findings reveal a knowledge gap on the safety of AADs, particularly in relation to cardiovascular adverse events, which were not mentioned in the SmPCs despite established concerns. Additionally, a disproportionality signal for pericardial disease was found for axitinib, but not mentioned in the drug's SmPC. Despite the exclusion of pharmacoepidemiological studies, this scoping review presents a novel approach to identify potential safety concerns of drugs and guide postmarketing surveillance of AADs.