cabozantinib versus everolimusMeteor

1. Original Article
Cabozantinib versus Everolimus in advanced
renal cell carcinoma (METEOR) : final results from
a randomised, open-label, phase 3 trial
Choueiri , T K , Escudier , B , Powles , T , Tannir , N M ,
Mainwaring , P N , Rini , B I , Hammers , H J , Donskov , F , Roth
, B J , Peltola , K , Lee , J L , Heng , D Y C , Schmidinger , M ,
Agarwal , N , Sternberg , C N , McDermott , D F , Aftab , D T ,
Hessel , C , Old , C S , Schwab , G , Hutson , T E , Pal , S ,
Motzer , R J
Lancet Oncology
Vol 17: 917–27
July 2016

2. Study Overview
• Cabozantinib is an oral inhibitor of tyrosine kinases including MET,
VEGFR, and AXL. The randomised phase 3 METEOR trial compared the
efficacy and safety of Cabozantinib versus the mTOR inhibitor
Everolimus in patients with advanced renal cell carcinoma who
progressed after previous VEGFR tyrosine-kinase inhibitor treatment.
• Here, we report the final overall survival results from this study based on
an unplanned second interim analysis.

3. Study Design
• Phase III trial
• Multicenter
• Open-label.
• controlled.
• Randomized
• 2016.
• The Lancet Oncology

4. Methods
• 658 patients.
• 18 years and older
• advanced or metastatic clear-cell renal cell carcinoma(amRCC).
• measurable disease.
• previous treatment with one or more VEGFR tyrosine-kinase
inhibitors.

5. Methods
• 1:1 ratio
• 2 Groups :
• 1-60 mg Cabozantinib once a day.
• 2-10 mg Everolimus once a day.

6. Methods

7. End Points
• Primary endpoint:
• Progression-free survival (PFS).
• Secondary endpoints:
• Overall survival (OS).
• Objective Response Rate (ORR).
• Safety.

8. METEOR : Baseline Characteristics

9. METEOR : Baseline Characteristics

10. Study Results

11. Primary End Point (PFS)
49
%

12. Secondary End Points

13. Secondary End Point (OS)
44
%
16.5
21.4

14. Secondary End Point (ORR)
17.0%
3.0%
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
14.0%
16.0%
18.0%
ORR
Response Rate
Cabozantinib Everolimus

15. Secondary End Point (Safety)
21.0%
63.0%
8.0%
32.0%
52.0%
8.0%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
Any AE (1-2) Any AE (Grade3) Any AE (Grade4)
Cabozantinib Everolimus

16. METEOR : Conclusions
• Treatment with Cabozantinib increased overall
survival, delayed disease progression, and
improved the objective response compared with
Everolimus.
• Based on these results, Cabozantinib should be
considered as a new standard-of-care treatment
option for previously treated patients with
advanced renal cell carcinoma.
• Patients should be monitored for adverse events
that might require dose modifications.

17. Original Article
Outcomes based on age in the phase III METEOR
trial of Cabozantinib versus Everolimus in patients
with advanced renal cell carcinoma
Frede Donskov,*, Robert J. Motzer, Eric Voog, Elizabeth Hovey,
Carsten Gru¨ llich, Louise M. Nott, Katharine Cuff, Thierry Gil, Niels
Viggo Jensen, Christine Chevreau, Sylvie Negrier, Reinhard
Depenbusch, Lothar Bergmann, Izzy Cornelio, Anne Champsaur,
Bernard Escudier, Sumanta Pal, Thomas Powles, Toni K. Choueiri
European Journal of Cancer
126 (2020) 1-10
27 December 2019

18. Study Overview
• Cabozantinib improved progression-free survival (PFS), overall survival
(OS) and objective response rate (ORR) compared with Everolimus in
patients with advanced renal cell carcinoma (RCC) after prior
antiangiogenic therapy in the phase III METEOR trial.
• Limited data are available on the use of targeted therapies in older
patients with advanced RCC.

19. End Points
• Primary endpoint:
• Progression-free survival (PFS).
• Secondary endpoints:
• Overall survival (OS).
• Objective Response Rate (ORR).
• Safety.

20. Study Results

21. Primary End Point (PFS)
47
%

22. Primary End Point (PFS)
47
%

23. Primary End Point (PFS)
62
%

24. Secondary End Points

25. Secondary End Point (OS)
28
%

26. Secondary End Point (OS)
34
%

27. Secondary End Point (OS)
43
%

28. Secondary End Point (ORR)
15.0%
21%
19%
5.0%
2%
0%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
Age <65 years Age, 65-74 years Age, >75 years
Response Rate
Cabozantinib Everolimus

29. Secondary End Point (Safety)
68.0%
75%
78%
60.0% 60% 58%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
Age <65 years Age, 65-74 years Age, >75 years
Safety
Cabozantinib Everolimus

30. Conclusion
• Cabozantinib improved PFS, OS and ORR
compared with Everolimus in previously treated
patients with advanced RCC, irrespective of age
group, supporting use in all age categories.
Proactive dose modification and supportive care
may help to mitigate AEs in older patients while
maintaining efficacy.

31. Original Article
Outcomes based on prior therapy in the phase 3
METEOR trial of Cabozantinib versus Everolimus
in advanced renal cell carcinoma
Thomas Powles, Robert J. Motzer, Bernard Escudier, Sumanta Pal, Christian
Kollmannsberger, Joanna Pikiel, Howard Gurney,Sun Young Rha, Se Hoon
Park, Poul F. Geertsen, Marine Gross-Goupil, Enrique Grande, Cristina
Suarez, David W. Markby, Alan Arroyo, Mark Dean, Toni K. Choueiri
British Journal of Cancer
(2018) 119:663–669
10 September 2018

32. Study Overview
• In the phase 3 METEOR trial, Cabozantinib improved progression-free
survival (PFS), objective response rate (ORR), and overall survival (OS)
versus Everolimus in patients with advanced renal cell carcinoma (RCC),
after prior antiangiogenic therapy. METHODS: Outcomes were evaluated
for subgroups defined by prior therapy with sunitinib or pazopanib as the
only prior VEGFR inhibitor, or prior anti-PD-1/PD-L1 therapy.

33. Study Results

34. Primary End Point (PFS)
47
%

35. Primary End Point (PFS)
33
%

36. Primary End Point (PFS)
78
%

37. Secondary End Points

38. Secondary End Point (OS)
34
%

39. Secondary End Point (OS)
34
%

40. Secondary End Point (OS)
44
%

41. Secondary End Point (ORR)
16.0%
19%
22%
3.0%
4%
0%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
Prior sunitinib Prior pazopanib Prior anti–PD-1/PD-
L1
Response Rate
Cabozantinib Everolimus

42. Secondary End Point (Safety)
67.0%
73%
83%
61.0% 62% 64%
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
80.0%
90.0%
Prior sunitinib Prior pazopanib Prior anti–PD-1/PD-
L1
AE Grade 3 or 4
Cabozantinib Everolimus

43. Conclusion
• Cabozantinib was associated with improved
clinical outcomes versus Everolimus in patients
with advanced RCC, irrespective of prior therapy,
including checkpoint inhibitor therapy.

44. Original Article
Quality of Life Outcomes for Cabozantinib Versus
Everolimus in Patients With Metastatic Renal Cell
Carcinoma: METEOR Phase III Randomized Trial
David Cella, Bernard Escudier, Nizar M. Tannir, Thomas Powles,
Frede Donskov, Katriina Peltola, Manuela Schmidinger, Daniel Y.C.
Heng, Paul N. Mainwaring, Hans J. Hammers, Jae Lyun Lee, Bruce J.
Roth, Florence Marteau, Paul Williams, John Baer, Milan Mangeshkar,
Christian Scheffold, Thomas E. Hutson, Sumanta Pal, Robert J.
Motzer, and Toni K. Choueiri
American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
VOLUME 36 • NUMBER 8
MARCH 10, 2018

45. Study Overview
• In the phase III METEOR trial, 658 previously treated patients with
advanced renal cell carcinoma were randomly assigned 1:1 to receive
Cabozantinib or Everolimus. The Cabozantinib arm had improved
progression-free survival, overall survival, and objective response rate
compared with Everolimus. Changes in quality of life (QoL), an
exploratory end point, are reported here.

46. Study Results

47. Secondary End Point (QOL)
Functional Assessment of Cancer (FKSI (19-
item))

48. Secondary End Point (QOL)
Functional Assessment of Cancer Disease-Related Symptoms (FKSI-DRS
(nine-item)

49. Secondary End Point (QOL)
Effect of baseline FKSI-DRS on OS

50. Conclusion
• In patients with advanced renal cell carcinoma,
relative to Everolimus, Cabozantinib generally
maintained QoL to a similar extent. Compared
with Everolimus, Cabozantinib extended Time to
deterioration (TTD) overall and markedly
improved TTD in patients with bone metastases.

51. Original Article
Long-term follow-up of overall survival for
Cabozantinib versus Everolimus in advanced
renal cell carcinoma
Robert J. Motzer1, Bernard Escudier2, Thomas Powles3, Christian
Scheffold4 and Toni K. Choueiri
British Journal of Cancer
(2018) 118:1176–1178
26 March 2018

52. Study Overview
• In the phase 3 METEOR trial (NCT01865747), Cabozantinib significantly
improved progression-free survival, overall survival, and objective
response rate compared with Everolimus in patients with advanced renal
cell carcinoma (RCC) after prior antiangiogenic therapy. A statistically
significant improvement in overall survival was observed at a second
interim analysis with 320 recorded deaths.

53. Study Results

54. Secondary End Point (OS)
30
%

55. Secondary End Point (Safety)
71.0%
61.0%
56.0%
58.0%
60.0%
62.0%
64.0%
66.0%
68.0%
70.0%
72.0%
AE 3 or 4
Safety
Cabozantinib Everolimus

56. Conclusions
• Cabozantinib significantly improved overall survival compared
with Everolimus in previously treated patients with advanced
RCC with consistent results after long-term follow-up.