26 / 27
stroma predicts benefit to
pembrolizumab in bladder cancer
0
20
40
60
80
100
pT0
Non-pT0
PD-L1 CPS (%)
Figure S3
-2
0
2
4
6
5
10
15
20
Figure S4
TMB (mutations/Mb)
Log (odds ratio)
provided in the Data Supplement). In addition, tumors that
harbored
PBRM1
mutations had signi
fi
cantly higher median TMB
values than did those without them (16.7 mut/Mb
v
10.5 mut/Mb;
P
= .001). The logistic model could not be applied as a result of the
small numbers.
Gene expression analyses demonstrated that 18 of 22 genes
from pT0 patients had signi
fi
cantly higher expressions in pre-
therapy lesions compared with those from pT
$
2 patients (Data
Supplement). Informative genes were those involved in interferon
gamma signaling, antigen presentation (HLA molecules and
immunoproteasome subunits), T-cell functional differentiation to
cytolytic effectors, chemokines and chemokine receptors, in-
hibitory receptors and ligands, and the immunosuppressive gene
IDO1
.
Fourteen patients among those with a postpembrolizumab
pT2 stage tumor or higher had paired tissue samples that were
evaluable for comparison after quality check. Postpembrolizumab
Table 3.
Pathologic Response to Pembrolizumab
Response
All Treated
Patients
(N = 50)
PD-L1 CPS
$
10% (n = 35)
PD-L1 CPS
,
10% (n = 15)
Primary end point
Pathologic complete
response, No. (%)
21 (42)
19 (54.3)
2 (13.3)
95% CI
28.2 to 56.8
Secondary end point
Pathologic
downstaging
to pT
,
2, No. (%)
27 (54)
23 (65.7)
4 (26.7)
95% CI*
39.3 to 68.2
Treatment failure, No. (%)
pT2N0
2 (3.8)
pT3-4N0
6 (12)
pTanyN+
10 (20)
Additional MVAC
chemotherapy
†
5 (10)
RECIST v1.1 PD
0
Necchi et al
Necchi, A et al, J Clin Oncol 2018
Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With
Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm,
Phase II Study N=50
ü
pT0 was achieved in 19 patients (54.3%) with PD-L1 CPS ≥10% compared with 2 patients
(13.3%) with CPS <10% (P = .011)
ü
A significant (P = .022) nonlinear association between TMB and pT0 response was found
(cutoff TMB > 15 mut/Mb)