Metastatic renal cell cancer and first-line combinations: for which patients? (focus on tolerance and health-related quality of life)

Until recently, the first-line treatments used in metastatic renal cell carcinoma were based on first-generation anti-VEGFR (vascular endothelial growth factor receptor) tyrosine kinase inhibitors (TKIs) as monotherapy. Trials combining immunotherapy (IO) (anti-CTLA4 + anti-PD-1) or immunotherapy with TKIs showed striking results in the first-line setting with improvement in overall response rates, progression-free survival and overall survival versus sunitinib. This allowed the combinations to gain registration in the US and Europe in the first-line advanced or metastatic clear-cell renal cell carcinoma setting. However, this improved activity comes at the cost of increased toxicity. Immunotherapy-related toxicities usually occur earlier within the first six months. With immunotherapy came a new range of toxicities making it more necessary to work with networks of specialists to better address autoimmune toxicity in particular. The safety profile is also impacted by the type of TKI used. In most cases, health-related quality of life (HRQoL) favours combinations over the comparator sunitinib. This article aims to review and assess the safety and HRQoL data on these new combinations.