Debate in RCC (Pembro axitinib versus Pembro Lenvatinib)

1. DEBATTLE: Pembrolizumab + Axitinib in first line treatment of
clear cell RCC
Khaled Abdel-Aziz Kamal
Ain Shams University
MERSAL Oncology Center

2. Disclosure
• Compensated advisory boards/Consultancy and/or speakers remuneration: Roche, MSD, Janssen,
Sanofi, AstraZeneca, Bayer, Novartis, Eva-Lilly, Sandoz, Merck Serono, Pfizer
• Meeting travel support: Roche, Janssen, Astrazeneca, Sanofi, Amgen, Astellas, Pfizer, Astellas
• Clinical trial involvement: Roche, AstraZeneca, Novartis

6. KEYNOTE-426 Study Design
Key Eligibility Criteria
Pembrolizumab 200 mg IV Q3W
for up to 35 cycles
+
Axitinib 5 mg orally twice dailyb
• Newly diagnosed or recurrent
stage IV clear cell RCC
No previous systemic treatment
for advanced disease
Karnofsky Performance Status
≥70
Measurable disease per
RECIST v1.1
Tumor sample for biomarker
Adequate organ function
N = 432 (62)a
•
• R
1:1
•
Sunitinib 50 mg orally once daily
for first 4 weeks of each 6-week
cyclec
•
•
N = 429 (68)a
Stratification Factors
• IMDC risk group (favorable vs intermediate vs poor)
• Geographic region (North America vs Western Europe vs ROW)
ange, 24.6-37.7)
• Sunitinib: 29.9 months (range, 24.6-37.9)
aNumber of East Asian patients in parentheses. bAxitinib dose could be increased to 7 mg, then 10 mg, twice daily if safety criteria were met; dose could be reduced to 3 mg, then 2 mg, twice daily to
manage toxicity. cSunitinib dose could be decreased to 37.5 mg, then 25 mg, once daily for the first 4 weeks of each 6-week cycle to manage toxicity.
Rini BI et al. N Engl J Med. 2019;380:1116-1127.
Median Follow-Up in East Asian Population
• Pembrolizumab + axitinib: 29.8 months (r
• Sunitinib: 29.9 months (range, 24.6-37.
Secondary End Points
• Key: ORR per
RECIST v1.1 by BICR in
ITT population
• Other: DOR per
RECIST v1.1, PROs,
safety
Primary End Points
• OS and PFS per
RECIST v1.1 by BICR in
ITT population

7. Baseline Characteristics
Sex
Male
Female
Age
<65 years
≥65 years
Karnofsky Performance Status
90/100
70/80
IMDC risk category
Favorable
Intermediate/poor
Sarcomatoid feature
Yes No
Unknown/missing
PD-L1 status
CPS ≥1
CPS <1
308 (71)
124 (29)
320 (75)
109 (25)
46 (74)
16 (26)
52 (76)
16 (24)
260 (60)
172 (40)
278 (65)
151 (35)
33 (53)
29 (47)
37 (54)
31 (46)
346 (80)
85 (20)
341 (79)
88 (21)
55 (89)
7 (11)
62 (91)
6 (9)
138 (32)
294 (68)
131 (31)
298 (69)
27 (44)
35 (56)
21 (31)
47 (69)
51 (12)
234 (54)
147 (34)
54 (13)
239 (56)
136 (32)
9 (15)
40 (65)
13 (21)
6 (9)
53 (78)
9 (13)
242 (56)
165 (38)
254 (59)
156 (36)
36 (58)
26 (42)
41 (60)
25 (37)
Not available/missing 25 (6) 20 (5) 0 2 (3)
aGlobal includes East Asian patients. bCPS is the number of PD-L1–staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100.
1. Powles T, et al. Lancet Oncol. 2020: in press. Data cutoff: January 6, 2020.
n (%)
Global1,a
East Asia
Pembrolizumab + Axitinib Sunitinib Pembrolizumab + Axitinib Sunitinib
n = 432 n = 429 n = 62 n = 68

8. OS in the ITT Population

9. Favorable Risk Intermediate / High
Risk
OS according to risk

10. Overall Survival comparison
• Keynote-426
• CLEAR Study

11. Baseline ccc comparison
• Keynote-426 • CLEAR Study

12. Axitinib / Pembro Lenvatinib / Pembro

13. PFS in ITT Population

14. Objective Response Rate

15. Duration of Response
69%
48% Global
100
90
80
70
60
50
40
30
20
10
0
24
0 6 18 30 42
12 36
Months
No. at risk
P + A
S
6
2
40 34 26 18 2 0
0
0
0
30 16 11 4 0
Kaplan-Meier curve is of the East Asian population. + indicates there was no progressive disease at the time of last disease assessment. aGlobal includes East Asian patients.
1. Powles T, et al. Lancet Oncol. 2020: in press. Data cutoff: January 6, 2020.
Remaining
in
Response,
%
43%
29%
Median (range), mo 24-Month Rate,%
1,a
23.5 (1.4+ to 34.5+) 47
15.9 (2.3 to 31.8+) 38
East Asia 18.2 (4.2 to 34.5+) 43
9.9 (2.8+ to 28.8+) 29

16. Summary of Adverse Events
Any-grade AE
Any-grade treatment-related AE
Grade 3-5 AE
Grade 3-5 treatment-related AE
Serious AE
Serious treatment-related AE
Deaths
Deaths due to a treatment-related AE
Discontinued any drug owing to a
treatment-related AE
Discontinued pembrolizumab
Discontinued axitinib
422 (98.4)
413 (96.3)
348 (81.1)
287 (66.9)
215 (50.1)
122 (28.4)
19 (4.4)
4 (0.9)
425 (100.0)
415 (97.6)
327 (76.9)
265 (62.4)
161 (37.9)
67 (15.8)
17 (4.0)
6 (1.4)
62 (100.0)
61 (98.4)
51 (82.3)
43 (69.4)
41 (66.1)
29 (46.8)
2 (3.2)
0
67 (100.0)
67 (100.0)
55 (82.1)
50 (74.6)
30 (44.8)
11 (16.4)
2 (3.0)
0
133 (31.0) 53 (12.5) 28 (45.2) 14 (20.9)
92 (21.4)
84 (19.6)
NA
NA
16 (25.8)
22 (35.5)
NA
NA
Discontinued pembrolizumab and axitinib 28 (6.5) NA 7 (11.3) NA
aGlobal includes East Asian patients. 1. Powles T, et al. Lancet Oncol. 2020: in press. Data cutoff: January 6, 2020.
n (%)
Global1,a
East Asia
Pembrolizumab + Axitinib Sunitinib Pembrolizumab + Axitinib Sunitinib
n = 429 n = 425 n = 62 n = 67

18. Treatment-RelatedAdverse Events
Incidence ≥20% Within Either Treatment Arm in the Global Population
Global1,a
Pembro + Axitinib (n = 432) Sunitinib (n = 429)
Any
Diarrhea
Hypertension
Hypothyroidism
PPE
Fatigue
Decreased appetite
Nausea
ALT increased
AST increased
Stomatitis
Mucosal inflammation
Dysgeusia
Dysphonia
Thrombocytopenia
Neutropenia
−100 −80 −60 −40 −20 0 20 40 60 80 100 −100 −80 −60 −40 −20
Incidence, %
aGlobal includes East Asian patients. 1. Powles T, et al. Lancet Oncol. 2020: in press. Data cutoff: January 6, 2020.

20. Thank you