When is immunotherapy too much? The case of favorable-risk metastatic renal cell carcinoma

Combination therapies integrating immune checkpoint inhibitors (ICIs) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), or dual ICI regimens, currently represent the standard of care for advanced clear cell renal cell carcinoma (ccRCC). However, in most favorable-risk patients according to the IMDC classification—particularly those with a low disease burden and without disease-related symptoms—first-line monotherapy with VEGFR-TKIs remains a valid option. This review summarizes the preclinical and clinical evidence supporting this approach, with the aim of guiding oncologists in personalizing therapy while minimizing overtreatment and toxicity.