Aprepitant in the Management of Immune Checkpoint Inhibitors Pruritus in Solid Cancer Patients

Pruritus, commonly known as itching, is an unpleasant sensation that triggers the urge to scratch, which may provide temporary relief. Pruritus can be intermittent or persistent, localized or widespread, and may be associated with medication use. Chronic pruritus, defined as lasting more than six weeks, can significantly affect sleep and quality of life. Dermatologic toxicities are among the most common immune-related adverse events (irAEs), reported in 43-45% of patients receiving ipilimumab and approximately 34% of those treated with nivolumab or pembrolizumab. Combination therapies (ipilimumab+ nivolumab or pembrolizumab) tend to elevate the incidence of potential irAEs to 41%. These toxicities typically emerge within the first few weeks of treatment, though delayed-onset cases have been documented. Cutaneous irAEs occur more rapidly in patients receiving combination therapy compared to anti-PD1 monotherapy. Pruritus is one of the most frequently observed cutaneous irAEs. Current treatments for pruritus are often inadequate, leaving many patients suffering from persistent and debilitating symptoms. Despite available therapies, a significant number of individuals continue to experience chronic itch that negatively impacts their quality of life. Substance P (SP) functions as a neurotransmitter and neuromodulator in the central and peripheral nervous systems of mammals. It is produced by both neuronal and non-neuronal cells and plays a role in various physiological responses, including nausea, depression, vomiting, pain, neurogenic inflammation, and, more recently, pruritus. SP exerts its biological effects primarily through neurokinin receptors (NKRs), also known as tachykinin receptors. When SP binds to NK1R in the skin, it triggers mast cell degranulation, leading to the release of pruritogenic and proinflammatory mediators such as histamine, interferon-γ, leukotriene B4, vascular endothelial growth factor (VEGF), and nerve growth factor (NGF). This results in