Kidney Cancer Journal 55
disease following surgery); 129 patients were enrolled,
and the trial was unblinded after 83 DFS events had been
observed. The median follow-up from randomization
was 30 months (with a range of 0.4 – 66.5 months). The
study did not meet the primary endpoint: hazard ratio
(95% CI) for DFS was 0.85 (0.55, 1.31) p= 0.47 in favor of
pazopanib. At the time of unblinding, 22/129 (17%) of
subjects had died. The hazard ratio for overall survival
was 2.65 (1.02, 6.9) in favor of placebo (p= 0.05). Appleman
concluded that adjuvant pazopanib in patients rendered
NED following metastasectomy did not improve
DFS compared to placebo and there was a trend toward
worse overall survival with pazopanib.
New Data Support Active Surveillance
in Selected Patients
Active surveillance is commonly practiced in mRCC patients
with asymptomatic, low-volume, slow growing
disease, although little evidence around this strategy
exists to support it. Canadian investigators, Igal Kushnir
and colleagues sought to remedy this by analyzing data
from the Canadian Kidney Cancer Information System
database. They identified 863 patients who underwent
active surveillance instead of immediate systemic therapy.
Of these, 370 started treatment 6 months after their initial
diagnosis and 493 never received systemic treatment
and were alive for 1 year. The median time on active
surveillance was 14.2 months (range 6 – 71), suggesting
that for a select group of patients, systemic therapy may
safely be delayed.
Emerging Trials to Watch With Novel Strategies
A few interesting trials in progress were showcased,
among them Nizar Tannir’s multicenter, randomized,
open-label phase 3 study (NCT03729245) with Nektar
Therapeutics which will evaluate the efficacy and safety
of bempegaldesleukin (NKTR-214) plus nivolumab compared
with investigator’s choice of first-line TKI (either
sunitinib or cabozantinib) in patients with previously untreated
advanced or metastatic RCC with clear cell component.
Another trial in progress highlighted was Alliance’s
A031704, also known as PDIGREE, which is an adaptive
phase 3 trial, in which clear cell RCC patients will be treated
with upfront nivolumab and ipilumumab. After completing
this treatment patients will be randomized based
on imaging response. Those who achieve a complete response
after nivolumab and ipilimumab will undergo
maintenance nivolumab, while patients with progressive
disease will switch to daily cabozantinib, and patients
with either partial response or stable disease will be randomized
to either nivolumab maintenance or nivolumab
with daily cabonzantinib.
Updates to ECOG-ACRIN 8143, the PROSPER study
were shared. In this global, unblinded, phase 3 study, patients
with any histology of RCC and clinical stage T2
or any T stage disease with positive lymph nodes are randomized
to receive 1 dose of nivolumab prior to complete
resection, followed by an additional 9 doses of adjuvant
nivolumab (480mg given every 4 weeks). The control arm
undergoes standard nephrectomy followed by observation
only. Oligometastatic disease is permitted if those
patient’s disease can be completely resected with metastasectomy.
The study was amended to enhance accrual
and patient quality of life (changing nivolumab to the
480mg every 4 weeks dose, for example) and amended a
requirement for baseline tumor biopsy, now only in the
nivolumab arm.
ASCO 201brought us incremental data that continue
to refine care for patients with advanced RCC, especially
for those with variant histologies and receiving immunotherapies,
ultimately improving survival. KCJ