immunotherapy.79 Previous studies have demonstrated that overexpression of PD-L1 leads to
worse outcomes and poor prognosis in patients
with RCC.80 Nivolumab, a fully human IgG4
PD- 1 immune checkpoint inhibitor, blocks the
interaction between PD- 1 and its ligands, PD-L1
and PD-L2. In a randomized, open-label, phase
3 study comparing nivolumab with everolimus
in patients with RCC who had previously undergone treatment with other standard therapies,
Motzer and colleagues81 demonstrated a longer
overall survival time and fewer adverse effects
with nivolumab. In this study, 821 patients
with clear-cell RCC were randomly assigned to
receive nivolumab ( 3 mg/kg of body weight
IV every 2 weeks) or everolimus ( 10 mg orally
once daily). The median overall survival time
with nivolumab was 25 months versus 19. 6
months with everolimus (P < 0.0148). Nineteen
percent of patients receiving nivolumab experienced grade 3 or 4 toxicities, with fatigue being
the most common adverse effect. Grade 3 or
4 toxicities were observed in 37% of patients
treated with everolimus, with anemia being the
most common. Based on the results of this trial,
on November 23, 2015, the U.S. Food and Drug
Administration approved nivolumab to treat
patients with metastatic RCC who have received
a prior antiangiogenic therapy.
Both TKI and mTOR inhibitor therapy fail,
and the patient is eligible for third-line therapy.
Because of his previous GI perforation, other
TKIs are not an option. The patient opts for
enrollment in hospice due to declining performance status. For other patients in this situation
with a good performance status, nivolumab
would be a reasonable option.
With the approval of nivolumab, multiple
treatment options are now available for patients
with metastatic or unresectable RCC. Develop-
ment of other PD- 1 inhibitors and immunother-
apies as well as multi-targeted TKIs will only serve
to expand treatment options for these patients.
Given the aggressive course and poor prognosis
of non-clear cell renal cell tumors and those with
sarcomatoid features, evaluation of systemic and
targeted therapies for these subtypes should re-
main active areas of research and investigation.
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