Conclusions: LEN + PEMBRO demonstrated promising
antitumor activity in pts with mccRCC with disease progression
following ICI therapy. No new safety signals
were detected. Efficacy outcomes by investigator review
per irRECIST. Clinical trial information: NCT02501096.
Research Funding: Eisai Inc., Woodcliff Lake, NJ, USA,
and Merck Sharp & Dohme Corp., a subsidiary of Merck
& Co. Inc., Kenilworth, NJ, USA
n Abstract 5020: Biomarker analysis and updated
clinical follow-up of preoperative ipilimumab (ipi)
plus nivolumab (nivo) in stage III urothelial cancer
(NABUCCO). Nick Van Dijk, Alberto Gil Jimenez, Karina
Silina et al.
Results: After a median FU of 15.6 months, 2 pts relapsed
(both non-pCR); 1 of these 2 pts died of metastatic
disease. Tumors showing complete response (CR, for
biomarker analysis defined as pCR, CIS or pTa) had a significantly
higher tumor mutational burden than non-
CR tumors. CR to ipi+nivo was independent of baseline
CD8 T-cell presence. There was no difference between
CR and non-CR tumors in baseline immune gene signatures,
such as interferon gamma and T-effector signatures.
Surprisingly, exploratory gene expression analysis
revealed that non-CR was associated with a baseline B
cell immune signature, particularly immunoglobulins
and genes involved in B cell receptor signaling. CD20
positive cells (by mIF) and presence of tertiary lymphoid
structures (TLS) at baseline were also associated with
non-CR. Upon treatment with ipi+nivo, early and mature
TLS increased significantly in responding tumors. A
subset of pts showed CR in the bladder, but non-CR in a
local LN tumor focus. WES revealed that these LN metastases
were genetically different from the primary tumor
bulk.
Conclusions: At 15.6 months follow-up, recurrence after
pre-operative ipi+nivo was low. Pathological complete
response was not restricted to tumors exhibiting preexisting
T cell immunity. Clinical trial information:
NCT03387761.
Research Funding: Bristol Meyers Squibb
n Abstract 5024: Association of gene expression
with clinical outcomes in patients with renal cell
carcinoma treated with pembrolizumab in
KEYNOTE-427. David F. McDermott, Jae-Lyun Lee, Frede
Donskov et al.
Results: Patient characteristics for this analysis were
comparable to the overall population. In cohort A, Tcell–
inflamed GEP (n = 78) was statistically significantly
associated with a better ORR (P = 0.021; AUROC = 0.65)
but not PFS (P = 0.116). No other TME canonical signatures
showed a correlation with ORR or PFS. ORR was estimated
for mutations (Table).
Conclusions: RNA-sequencing–based, T-cell–inflamed
GEP was associated with ORR in patients with clear cell
renal cell carcinoma receiving first-line pembrolizumab.
Precision was limited by sample size for estimating ORR
by specific gene mutation status. Evaluation of tissuebased
biomarkers in larger studies are planned. Biomarker
analyses from patients in cohort B will also be
presented. Clinical trial information: NCT02853344.
40 Kidney Cancer Journal
Research Funding: Merck Sharp & Dohme Corp., a sub
idiary of Merck & Co., Inc., Kenilworth, NJ, USA
n Abstract 5061: Association of neutrophil to
lymphocyte ratio (NLR) with efficacy from JAVELIN
Renal 101. Mehmet Asim Bilen, Brian I. Rini, Robert J.
Motzer et al.
Results: In the avelumab + axitinib arm, patients with <
median NLR (N = 217) had longer observed PFS (stratified
HR, 0.85; 95% CI, 0.634, 1.153) and longer observed
OS (stratified HR, 0.51; 95% CI, 0.300, 0.871) than patients
with median NLR (N = 217). The ORR was 57.1%
in patients with < median NLR vs 47.5% in patients with
median NLR, with complete response in 5.5% vs 1.4%.
Multivariate analysis showed that low NLR was associated
with longer PFS and OS by treating baseline NLR as
either a continuous variable or a binary variable (dichotomized
by median).
Conclusions: Low NLR was associated with better observed
treatment outcomes in patients with aRCC who
received avelumab + axitinib. Clinical trial information:
NCT02684006.
Research Funding: This study was funded by Pfizer, as
part of an alliance between Pfizer and Merck KGaA,
Darmstadt, Germany.
n Abstract 5080: Axitinib plus pembrolizumab in
patients with advanced renal cell carcinoma:
Long-term efficacy and safety from a phase Ib study.
Michael B. Atkins, Igor Puzanov, Elizabeth R. Plimack et al.
Results: At data cut-off date (July 3, 2019), median OS
was not reached; 38 (73.1%) patients were alive. 14
(26.9%) patients had died, none were related to treatment.
The probability of being alive was 96.1% (95% CI
85.2–99.0) at 1 year, 88.2% (95% CI 75.7– 94.5) at 2
years, 82.2 % (95% CI 68.5– 90.3) at 3 years, and 66.8 %
(95% CI 49.1–79.5) at 4 years. Median PFS was 23.5 (95%
CI 15.4–30.4) months. Median duration of response was
22.1 (95% CI 15.1–not evaluable) months. Median time
on treatment with the combination AXI/pembro was
14.5 months (n=52), median time on pembro after AXI
discontinuation was 9.0 months (n=10), and median
time on AXI after pembro discontinuation was 7.5
months (n=11). After stopping study treatment, 22 patients
received subsequent systemic therapy, including
nivolumab and cabozantinib (n=6 each). Grade 3/4 AEs
were reported in 38 (73.1%) patients. 20 (38.5%) patients
discontinued either drug due to AEs: 17 (32.7%) patients
discontinued AXI, and 13 (25.0%) patients discontinued
pembro with 10 (19.2%) discontinuing both drugs. Dose
reduction of AXI due to AEs was reported in 16 (30.8%)
patients. The most common AEs reported were diarrhea
(84.6%), fatigue (80.8%), hypertension (53.8%), cough
(48.1%), and dysphonia (48.1%). Increased alanine
aminotransferase and aspartate aminotransferase occurred
in 44.2% and 36.5% of patients, respectively.
With this longer follow-up, there were no cumulative
AEs or new AEs. OS by IMDC risk group will be presented.
Conclusions: In patients with advanced RCC with almost
5 years of follow-up, the combination of AXI/pembro
continues to demonstrate clinical benefit with no