In metastatic renal cell carcinoma (mRCC) the PD-1 immune-checkpoint inhibitor (ICI)
Nivolumab became a standard second line treatment option in 2015 based on a significant improvement
of overall survival compared to Everolimus. Current pivotal phase 3 studies showed that PD-1
ICI-based combinations were more efficacious than the VEGFR-TKI Sunitinib, a previous standard
of care, leading to approval of three new regimens as guideline-recommended first-line treatment.
Nivolumab plus Ipilimumab is characterized by a survival advantage, a high rate of complete
response and durable remissions in intermediate and poor prognosis patients. Despite frequent
immune-mediated side effects, fewer symptoms and a better quality of life were observed compared
to Sunitinib. Pembrolizumab or Avelumab plus Axitinib were characterized by an improved
progression-free-survival and a high response rate with a low rate of intrinsic resistance. In addition,
Pembrolizumab plus Axitinib reached a significant survival benefit. The side effect profile is driven
by the chronic toxicity of Axitinib, but there is additional risk of immune-mediated side effects of the
PD-1/PD-L1 ICIs. The quality of life data published so far do not suggest any improvement regarding
patient-reported outcomes compared to the previous standard Sunitinib. The PD-1/PD-L1 ICIs thus
form the backbone of the first-line therapy of mRCC
