6
Treatment
Recommendation 3.2
➤ All patients with metastatic clear cell renal cell carcinoma who
require systemic therapy in the first-line setting should undergo risk
stratification into IMDC favorable (0), intermediate (1–2), and poor
(3+) risk groups. Patients with intermediate or poor risk disease
should be offered combination treatment with two immune checkpoint
inhibitors (i.e., ipilimumab and nivolumab) or an immune checkpoint
inhibitor in combination with a VEGFR TKI. (Strong recommendation;
EB-B-H)
Recommendation 3.3
➤ Patients with favorable risk disease who require systemic therapy
may be offered an immune checkpoint inhibitor in combination with a
VEGFR TKI. (Strong recommendation; EB-B-H)
Recommendation 3.4
➤ Select patients with metastatic clear cell renal cell carcinoma
receiving systemic therapy in the first-line setting including those
with favorable risk disease or with certain co-existing medical
problems may be offered monotherapy with either a VEGFR TKI or an
immune checkpoint inhibitor. (Strong recommendation; EB-B-M)
Recommendation 3.5
➤ The use of high dose interleukin-2 (HD-IL2) may be considered in the
first-line systemic therapy setting for patients with metastatic clear
cell renal cell carcinoma (see Practical Information). Attempts to
develop criteria to predict those patients most likely to derive benefit
from HD-IL2 have been unsuccessful. (Weak recommendation; EB-
B-M)
a
Practical Information: The significant toxicity of this regimen must be weighed in
relation to the newer immunotherapy regimens which have largely replaced this
treatment. The expert panel was not able to identify a patient population who should
receive this treatment preferentially based on available data. The expert panel did
agree that HD-IL-2 should be administered in experienced high-volume centers, and
that enrollment in clinical trials was preferred.
a
See Figure 1: First-line Treatment.
Recommendation 4.1
➤ Nivolumab or cabozantinib should be offered to patients who
progressed on a VEGFR TKI alone. (Strong recommendation; EB-B-H)
Recommendation 4.2
➤ Patients progressing on combination immunotherapy (e.g., nivolumab,
ipilimumab) should be offered a VEGFR TKI. (Strong recommendation;
CB-B-M)
