Therapeutic approaches in non-clear

cell and clear cell RCC

Sylvie Rottey
Medical Oncologist
Clinical Pharmacologist
UZGent

RCC
Sylvie Rottey
Medical Oncologist
Gent University Hospital

Six risk factors IMDC:

Karnofsky performance status < 80%
Haemoglobin < lower limit of normal
Time from diagnosis to treatment < 1 year
Corrected calcium > upper limit of normal
Platelets > upper limit of normal
Neutrophils > upper limit of normal
0 Favorable / 1-2 Intermediate / 3-6 Poor prognosis

IMDC Prognostic Factors

23 months
Favorable
43 mons

Intermediate 23 mons
8 months
Poor 8 mons

Heng et al Lancet Oncology 2013

IMDC in non-clear cell RCC

Favorable 31.4 mons

Intermediate 16.1 mons
Poor 5.1 mons

Kroeger et al,
Cancer 2013
Kroeger et al Cancer 2013

ASPEN Trial

Andrew et al. JCO 2015

108 pts
Sunitinib versus everolimus in non-ccmRCC
PFS SU 8,3 mths EVE 5,6 mths HR 1,41
However PFS better with everolimus for
-poor risk
-chromophobe

CheckMate-025: phase III study of nivolumab vs everolimus in

locally advanced/mRCC with prior anti-angiogenic therapy1,2

Eligibility:

Advanced or mRCC
with clear-cell
component

Received 1 or 2 prior
anti-angiogenic
therapies

Progression on or after
most recent therapy
(within 6 months of
study enrolment)

Karnofsky PS 70

N=821

R
A
N
D
O
M
I
S
A
T
I
O
N

Nivolumab
3 mg/kg IV
every 2 weeks
Treatment until
disease
progression or
unacceptable
toxicity

1:1

Everolimus
10 mg orally daily

Primary endpoint: OS
Secondary endpoints: PFS, ORR, DOR, duration of OS in PD-L1-positive vs
PD-L1-negative subgroups, safety, disease-related symptom progression rate
Stratification: MSKCC risk criteria; number of prior anti-angiogenic therapies; region
1. www.clinicaltrials.gov (NCT01668784);
2. Motzer et al. NEJM 2015

Patient Characteristics

Nivolumab Group
(N = 410)

Everolimus Group
(N = 411)

Male

77

74

Female

23

26

Favourable

35

36

Intermediate

49

49

Poor

16

15

72

72

28

28

US/Canada

42

42

Western Europe

34

34

Rest of world

23

24

CheckMate-025: Patient demographics

62 (2388)
62 (1886)

Median age, years (range)

Sex, %

MSKCC risk group, %

Number of prior anti-angiogenic regimens in advanced

setting, %

Region, %

Motzer et al. NEJM 2015

Sharma et al. ECC 2015 Oral presentation 3LBA

CheckMate-025: OS

Minimum follow-up was 14 months

Motzer et al. NEJM 2015

CheckMate-025: PFS

Motzer et al. NEJM 2015

Antitumour activity

Nivolumab Group
(N = 410)

Everolimus Group
(N = 411)

25

CheckMate-025: Anitumour activity

ORR,%

5.98 (3.689.72)

Odds ratio (95% CI)

P value

<0.001

Best overall response,%

Complete response

<1

Partial response

24

Stable disease

34

55

Progressive disease

35

28

Not evaluated

12

Median time to response, months (range)

3.5 (1.424.8)

3.7 (1.511.2)

Median duration of response, months (range)*

12.0 (027.6)

12.0 (022.2)

49/103 (48)

10/22 (45)

Ongoing response, n/N (%)

*For patients without progression, duration of response is defined as the time from
first response date to date of censoring

Motzer et al. NEJM 2015

Motzer et al. NEJM 2015 Supplement

CheckMate-025: OS by subgroup analysis

Motzer et al. NEJM 2015

CheckMate-025: Safety summary

Nivolumab Group
(N = 406)

Treatment-related AEs, %
Treatment-related AEs leading to

discontinuation, %
Treatment-related deaths, n

Everolimus Group
(N = 397)

Any Grade

Grade 3 or 4

Any Grade

Grade 3 or 4

79

19

88

37

13

2*

44% of patients in the nivolumab arm and 46% of patients in the everolimus
arm were treated beyond progression

*Septic shock (1); bowel ischemia (1)

Motzer et al. NEJM 2015

Sharma et al. ECC 2015 Oral presentation 3LBA

CheckMate-025: Treatment-related AEs in 10%

of patients
Treatment-related AE, %

Nivolumab Group
(N = 406)
Any Grade
Grade 3 or 4

Everolimus Group
(N = 397)
Any Grade
Grade 3 or 4

All events

79

19

88

37

Fatigue

33

34

Nausea

14

<1

17

Pruritus

14

10

Diarrhoea

12

21

Decreased appetite

12

<1

21

Rash

10

<1

20

Cough

19

Anaemia

24

Dyspnoea

13

Peripheral oedema

14

Pneumonitis

15

Mucosal inflammation

19

Dysgeusia

13

Hyperglycaemia

12

Stomatitis

29

Hypertriglyceridemia

16

Epistaxis

10

0
Motzer et al. NEJM 2015

METEOR
- phase III
- 1 or 2
previous
therapies
- cc a/mRCC
- 650 pts

Study design

2010 Universitair Ziekenhuis Gent

Choueiri TK et al. Abstract 4LBA; Presented at ECCO - ESMO

18
2015.

METEOR
- phase III
- 1 or 2
previous
therapies
- cc a/mRCC
- 650 pts

Best target lesion change from baseline

2010 Universitair Ziekenhuis Gent

Choueiri TK et al. Abstract 4LBA; Presented at ECCO - ESMO

19
2015.

METEOR
- phase III
- 1 or 2
previous
therapies
- cc a/mRCC
- 650 pts

PFS

2010 Universitair Ziekenhuis Gent

OS

Choueiri TK et al. Abstract 4LBA; Presented at ECCO - ESMO

20
2015.

AEs

METEOR
- phase III
- 1 or 2
previous
therapies
- cc a/mRCC
- 650 pts

Choueiri TK et al. Abstract 4LBA;

Presented at ECCO - ESMO
2015.
2010 Universitair Ziekenhuis Gent

Choueiri TK et al. N Engl J Med

2015 [Epub ahead of print].
21

RCC
Sylvie Rottey
X
X

Medical Oncologist
Gent University Hospital

Therapeutic approaches in non-clear

cell and clear cell RCC
Sylvie Rottey
Medical Oncologist
Clinical Pharmacologist
UZGent