EURURO Vol. 72 No. 6

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survival (OS) was 12.8 versus 22.3 mo (p < 0.0001) . A
systematic review of RKC subpopulations from randomized
controlled trials (RCTs) had significantly lower response
rates and poorer median progression-free survival (PFS) and
OS when compared with the predominant ccRCC population
included in the same trials
A phase II study of everolimus in pRCC patients (RAPTOR)
reported clinical benefits; among patients with type 1 or
type 2 histology, median PFS was 7.9 and 5.1 mo,
respectively Two RCTs recruiting only RKC patients
compared sunitinib with everolimus (Everolimus Versus
Sunitinib Prospective Evaluation in Metastatic Non–clear
Table 1 – Randomized and single-arm phase 2 trials that reported outcome for various RKC subtypes
Trial
[Reference]
Patient
(n)
Subtypes
(n)
Treatment/
comparator
Line PFS (mo):[95% CI],
(HR [95% CI])
OS (mo)
[95% CI],
(HR [95% CI])
RECIST
response
ORR (%)
Randomized controlled trials
ASPEN
NCT01108445
108 pRCC 76/108
chRCC 16/108
uRCC
Everolimus (EVE)
versus sunitinib
(SUN)
First EVE: 5.6 [5.5–60]
SUN: 8.3 [5.8–11.4]
(1.41 [0.88–2.27])
EVE: 13.2 [9.7–37.9]
SUN: 31.5 [14.8–NA]
(1.12 [0.7–2])
EVE:
CR: 1
PR: 4
SD: 30
PD: 13
SUN:
CR: 0
PR: 9
SD: 30
PD: 10
EVE: 9%
SUN: 18%
ESPN
NCT01185366
68 pRCC 27/68
chRCC 12/68
TRCC
uRCC
Sarcomatoid
Everolimus (EVE)
versus sunitinib
(SUN)
First,
second
EVE: 4.1 [2.7–10.5]
SUN: 6.1[4.2–9.4]
(1.16 [0.67–2.01])
EVE: 14.9 [8.0–23.4]
SUN: 16.2 [14.2–NA]
(NA)
EVE:
CR: 0
PR: 1
SD: 24
PD: 8
SUN:
CR: 0
PR: 3
SD: 21
PD: 9
EVE: 3%
SUN: 11%
RECORD3
NCT00903175
66 pRCC 50/66
chRCC 12/66
uRCC
Everolimus (EVE)
versus sunitinib
(SUN)
First,
second
EVE: 5.1 [2.6–7.9]
SUN: 7.2 [5.4–13.8]
(1.5 [0.9–2.8])
NA NA NA NA
SWOG1107
NCT01688973
50 pRCC 50/50 Tivantinib (TIV)
versus tivantinib +
erlotinib (ERL)
First,
second
TIV: 2 [NA]
TIV + ERL: 5.4 [NA]
(NA)
TIV: 10.3 [NA]
TIV + ERL: 11.3 [NA]
(NA)
NA NA TIV: 0
TIV + ERL: 0
ARCC
NCT00065468
73 pRCC 55/73
uRCC
IFN-a versus
temsirolimus
(TEM)
First IFN-a: 1.8 [1.6–2.1]
TEM: 7 [3.9–8.9]
(0.38 [0.23–0.62])
IFN-a: 4.3 [3.2–7.3]
TEM: 11.6 [8.9–13]
(0.49 [0.29–0.85])
NA IFN-a: 12%
TEM: 12%
Single-arm studies
RAPTOR
NCT00688753
88 ITT/
92
pRCC type
1 14/88
pRCC type
2 43/88
Everolimus First Type 1: 7.9 [2.1–11.0]
Type 2: 5.1 [3.3–5.5]
(NA)
Type 1: 28.0 [7.6–NA]
Type 2: 24.2 [15.8–32.8]
(NA)
ITT:
CR: 0
PR: 1
SD: 57
PD: 28
ITT:1%
SUPAP
NCT00541008
61 pRCC type
1 15/61
pRCC type
2 46/61
Sunitinib First Type 1: 6.6 [2.8–14.8]
Type 2: 5.5 [3.8–7.1]
Type 1: 17.8 [5.7–26.1]
Type 2: 12.4 [8.4–14.3]
Type 1/2
CR: 0/0
PR: 2/5
SD: 10/25
PD: 3/16
NA
NCT01399918 35 pRCC 5/35
chRCC 5/35
RMC 2/35
uRCC 23/35
p-uRCC 14
uRCC 9
Bevacizumab +
everolimus
First All: 11.0 [3.8–19.3]
p-uRCC: 12.9 [10.9–NA]
uRCC: 1.9 [1.6–NA]
All: NA
p-uRCC: 28.9 [NA]
uRCC: 9.3 [NA]
All:
CR: 1
PR: 9
SD: 15
PD: 8
All: 29%
p-uRCC: 43%
uRCC: 11%
NCT00726323 74 pRCC any type Foretinib First,
second
9.3 [6.9–12.9] Not reached CR: 0
PR: 10
SD: 61
PD: 3
13.5%
NCT00422019 61 ccRCC 46/61
pRCC 7/61
chRCC 3/61
uRCC 5/61
AMG102 First,
second,
third
3.7 [1.8–7.6] 14.9 [9.4–NA] CR: 0
PR: 1
SD: 26
PD: 16
NA: 18
2.5%
NCT02127710 109 pRCC any type
MET+ 44/109
MET– 46/109
NA 19/109
Savolitinib First MET+: 6.2 [4.1–7.0]
MET–: 1.4 [1.4–2.7]
NA CR: 0
PR: 8
(all MET+)
SD: 43
PD: 48
NA: 10
MET+: 18%
MET–: NA
CI = confidence interval; CR = complete response; HR = hazard ratio; IFN-a = interferon alpha; ITT = intention to treat subgroup; pRCC = papillary renal cell
carcinoma; chRCC = chromophobe renal cell carcinoma; RMC = renal medullary carcinoma; ccRCC = clear-cell renal cell carcinoma; uRCC = unclassified renal
cell carcinoma; TRCC = translocation renal cell carcinoma; NA = not applicable; ORR = objective response rate; OS = overall survival; PD = progressive disease;
PFS = progression-free survival; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; RKC = rare kidney cancer; SD = stable disease.
a 80% CI.
b Subgroup of RKC.
E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 9 7 4 – 9 8 3 976