Metastatic renal cell carcinoma: Management of toxicities of combinations

New combinations of ontiongiogenic tyrosine kinose inhibitors (TKI) and immune checkpoint inhibitors (ICI) or dual ICI have been shown to be effective in phase trials compared to sunitinib in the first-line treatment of metastatic renal cell cancer. While ICI doublet is already used in other indicotions, TKI/ICI combinations are more recent and the management of their adverse effects (AEs) ore less well known, particularly with regard to the accountability of each therapeutic class. The objective of this article is to analyze the safety data from the main phase Ill studies to provide clinicians with practical advice for managing the AEs from these combinations. Their management depends largely on the type of combination and their grade. In the case of a TKI/ICI combination, discontinuation of the 2 molecules is considered from grade 2. Rapid improvement in symptoms suggests that the AE is related to the TM. It is then possible, after resolution, to reintroduce the TKI, if needed by reducing the dose, and to continue the ICI. Otherwise, the blame falls on the ICI and treatment usually involves corticosteroids. Management also depends on the type of AE ond its severity. In some coses (dysthyroidism), treatment with TKI/ICI may be continued. In other situations (cardiac or neurological toxicity), it should be discontinued from grade 1 and hospitalization and corticosteroid therapy should be considered immediately. In all cases, information and education ore integral parts of the prevention and proper management of potential AEs.