Presentación en el marco del lanzamiento de Nintedanib (Vargatef) para cáncer de pulmón, Santa Marta, 19.07.2019. Auspiciado por Boehringer-Ingelheim

1. KN189/IMpower150
How chemo-immunotherapy
changed the management of
NSCLC in first-line
Inspirado en: Armin Hofman, 1959, Cartel Giselle

2. Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA
Medellín
Inspirado en: Michael Bierut, 2013, Logo para Mohawk Fine Papers

3. Exposición
Acción
ascendente
Clímax
Desenlace
Pirámide de Freytag
Acción
descendente

4. Prophecy:
Son (Œ) will kill
Father (L)
Œ
abandoned
Œ
survives
Œ
encounters
L on the
road
ΠKills
L
Œ
encounters
Sphynx
ΠKills the
Sphynx
ΠMarries
Mamma (Y)
Πblinds himself
(Y hangs herself)
The End
Œdipus Rex

5. ѕυrvιval ѕaғeтy
qol coѕт

6. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado

7. Lung
cancer
kills
Older
(“Alkylating”)
Chemo
No OS benefit
over BSC
Cisplatin-based CT
Improves OS
Any
Doublet
will do
Bevacizumab + CT
Improves OS
Pemetrexed
also improves
OS
IO +/- CT +/- Bev
Improves OS
Most pts
with
Stage IV
NSCLC
Still die
NSCLC with no actionable mutations
1st-Line
9
12
15
18
1996 2006 20161986
Year
Median OS
(mo)

8. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado
Chemo + IO in
1st-line Non-
squamous
NSCLC

9. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado
Exhibit A
KN-189

10. Key Eligibility
Criteria
Untreated stage IV
nonsquamous NSCLC
No sensitizing EGFR
or ALK alteration
ECOG PS 0 or 1
Provision of a sample
for PD-L1 assessment
No symptomatic brain
metastases
No pneumonatisi
requiring systemic
steroids
Placebo (normal saline) +
Pemetrexed 500 mg/m2 +
Carboplatin AUC 5 OR
Cisplatin 75 mg/m2
Q3W for 4 cycles
Pembrolizumab 200 mg +
Pemetrexed 500 mg/m2 +
Carboplatin AUC 5 OR
Cisplatin 75 mg/m2
Q3W for 4 cycles
Pembrolizumab 200 mg Q3W for
up to 31 cycles
+
Pemetrexed
500 mg/m2 Q3W
Placebo (normal saline)
for up to 31 cycles
+
Pemetrexed
500 mg/m2 Q3W
Pembrolizumab
200 mg Q3W
for up to 35 cycles
R
2:1
On PD
Gandhi, AACR, 2018
KEYNOTE-189

11. Gandhi, AACR, 2018

12. Gandhi, AACR, 2018

13. Gandhi, AACR, 2018

14. Gandhi, AACR, 2018

15. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

16. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

17. THE FRAGILITY INDEX
Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

18. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

19. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
THE
NUMBER OF PATIENTS
REQUIRED TO LOSE STATISTICAL
SIGNIFICANCE

20. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
THE
NUMBER OF PATIENTS
REQUIRED TO LOSE STATISTICAL
SIGNIFICANCE

21. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm
THE
NUMBER OF PATIENTS
REQUIRED TO LOSE STATISTICAL
SIGNIFICANCE

22. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

23. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

24. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

25. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

26. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

27. Inspirado en: Saul Bass, 1955,, The Man With the Golden Arm

28. Walsch, J Clin Epidem, 2014
52
99
79
75
Event+
Event-
Control Experimental
p=0.004

29. 52
99
79
75
Event+
Event-
Control Experimental
p=0.004
53
98
p=0.005
+1
Walsch, J Clin Epidem, 2014

30. 52
99
79
75
Event+
Event-
Control Experimental
p=0.004
53
98
p=0.005
+1
54
97
p=0.007
+2
Walsch, J Clin Epidem, 2014

31. 52
99
79
75
p=0.004
53
98
p=0.005
+1
54
97
p=0.007
+2
55
96
p=0.01
+3
Walsch, J Clin Epidem, 2014

32. 52
99
79
75
p=0.004
53
98
p=0.005
+1
54
97
p=0.007
+2
55
96
p=0.01
+3
…
Walsch, J Clin Epidem, 2014

33. 52
99
79
75
p=0.004
59
92
p=0.04
+7
60
91
p=0.055
+8
…
Walsch, J Clin Epidem, 2014

34. 52
99
79
75
p=0.004
59
92
p=0.04
+7
60
91
p=0.055
+8
…
Fragility index: 8
Walsch, J Clin Epidem, 2014 https://clincalc.com/Stats/FragilityIndex.aspx

35. Gandhi, NEJM, 2018
“With 235 deaths in the intention-to-treat population, the
estimated proportion of patients who were alive at 12 months was
69.2% (95% confidence interval [CI], 64.1 to 73.8) in the
pembrolizumab-combination group and 49.4% (95% CI, 42.1 to
56.2) in the placebo-combination group. The median overall
survival was not reached in the pembrolizumab-combination
group and was 11.3 months (95% CI, 8.7 to 15.1) in the placebo-
combination group (hazard ratio for death, 0.49; 95% CI, 0.38 to
0.64; P<0.001)”

36. Gandhi, NEJM, 2018
Fragility index:
41

37. Gandhi, AACR, 2018
Fragility index: 41

38. Gandhi, NEJM, 2018

39. CT + Pembro
also benefited
PD-L1<1%
Gandhi, NEJM, 2018

40. Gandhi, NEJM, 2018

41. Gandhi, NEJM, 2018

42. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado
Exhibit B
IMpower150

43. Key Eligibility Criteria
Untreated stage IV or
recurrent non-
squamous NSCLC
Chemotherapy-naïve
ECOG PS 0 or 1
Provision of a sample
for PD-L1 and
biomarker assessment
Arm B
Atezolizumab +
Carboplatin + Paclitaxel
+ Bevacizumab
4 or 6 cycles
Arm A
Atezolizumab +
Carboplatin + Paclitaxel
4 or 6 cycles
Atezolizumab
Atezolizumab
+
Bevacizumab
R
1:1:1
Reck, ESMO, 2017
IMpower150
Arm C (control)
Carboplatin + Paclitaxel
+ Bevacizumab
4 or 6 cycles
Bevacizumab

44. Arm B
Atezolizumab +
Carboplatin + Paclitaxel
+ Bevacizumab
4 or 6 cycles
Atezolizumab
+
Bevacizumab
Arm C (control)
Carboplatin + Paclitaxel
+ Bevacizumab
4 or 6 cycles
Bevacizumab
Key Eligibility Criteria
Untreated stage IV or
recurrent non-
squamous NSCLC
Chemotherapy-naïve
ECOG PS 0 or 1
Provision of a sample
for PD-L1 and
biomarker assessment
R
1:1:1
Reck, ESMO, 2017
IMpower150

45. Reck, ESMO, 2017
Only wild-type

46. Reck, NEJM, 2018
Only wild-type

47. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado

48. Reck M, JCO, 2018
Fragility index:
5

49. Reck M, JCO, 2018
EGFR and ALK mutated
were included
(10% and 4%, respectively)

50. Reck, NEJM, 2018

51. Reck, NEJM, 2018
The phase 3 IMpower150 study showed that the
addition of atezolizumab to bevacizumab plus
chemotherapy as first-line treatment for
nonsquamous metastatic NSCLC resulted in a
significant improvement in progression-free
survival and overall survival, regardless of PD-L1
expression and EGFR or ALK genetic alteration
status

52. MLM
Meta-analysis

53. Created by Mauricio Lema with RevMan5, 2019
Chemo + IO vs Chemo in 1st-line Stage IV Non-squamous NSCLC

54. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado
Chemo vs IO
in 1st-line in
NSCLC

55. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado
Exhibit A
PD-L1 ≥50%
KN-024

56. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado

57. Key Eligibility
Criteria
Untreated stage IV
NSCLC
No sensitizing EGFR
or ALK alteration
ECOG PS 0 or 1
PD-L1 ≥ 50%
No symptomatic brain
metastases
No significant
glucocorticoid or
immunosuppressive
therapy
Platinum-based chemotherapy
Q3W for 4 x 6 cycles
Pembrolizumab 200 mg
Q3W for 35 cycles
Pemetrexed maintenance,
allowed
Pembrolizumab
200 mg Q3W
for up to 35 cycles
R
1:1
On PD
Reck M, NEJM, 2016
KEYNOTE-024

58. Reck M, JCO, 2018
Squamous
histology were
included (18%)

59. Reck M, NEJM, 2016

60. Reck M, JCO, 2018

61. Inspirado en: Josef Albers, 1967, Homenaje al cuadrado

62. Reck M, JCO, 2018
Fragility index:
19

63. Reck M, JCO, 2018
Fragility index: 19

64. Mok, Lancet, 2019
Exhibit B
PD-L1+
KN-042

65. Key Eligibility Criteria
Untreated stage IV
NSCLC
No sensitizing EGFR
or ALK alteration
ECOG PS 0 or 1
PD-L1 ≥ 1%
No symptomatic brain
metastases
No significant
glucocorticoid or
immunosuppressive
therapy
Platinum-based chemotherapy
Q3W for 4 x 6 cycles
Pembrolizumab 200 mg
Q3W for 35 cycles
Pemetrexed maintenance,
allowed
R
1:1
Mok, Lancet, 2019
KEYNOTE-042

66. Squamous
histology were
included (37%)

67. Mok, Lancet, 2019
PD-L1 ≥50%

68. Mok, Lancet, 2019
PD-L1 ≥20%

69. Mok, Lancet, 2019
PD-L1 ≥1%

70. Mok, Lancet, 2019
mOS (mo)
PD-L1
≥50%
PD-L1
≥20%
PD-L1
≥1%
Pembr. 20 17.7 16.7
Chemo. 12.2 13.0 12.1

71. Mok, Lancet, 2019

72. Mok, Lancet, 2019
PD-L1 ≥1-49%

73. Mok, Lancet, 2019
mOS
(mo)
PD-L1
≥50%
PD-L1
≥20%
PD-L1
≥1%
PD-L1
≥1-49%
Pembr. 20 17.7 16.7 13.4
Chemo. 12.2 13.0 12.1 12.1

74. Single-agent Pembrolizumab
not supported in PD-L1
negative

75. Mok, Lancet, 2019
PFS

76. Mok, Lancet, 2019
PD-L1 ≥50%

77. Mok, Lancet, 2019
PD-L1 ≥50%

78. Mok, Lancet, 2019
PD-L1 ≥20%

79. Mok, Lancet, 2019
PD-L1 ≥20%

80. Mok, Lancet, 2019
PD-L1 ≥1%

81. Mok, Lancet, 2019
PD-L1 ≥1%

82. Mok, Lancet, 2019
PFS PD-L1 ≥1%
OS PD-L1 ≥1%
PFS PD-L1 ≥1-49%
OS PD-L1 ≥1-49%
PFS PD-L1 ≥50%
OS PD-L1 ≥50%
KN-042

83. Mok, Lancet, 2019
PFS PD-L1 ≥1%
OS PD-L1 ≥1%
PFS PD-L1 ≥1-49%
OS PD-L1 ≥1-49%
PFS PD-L1 ≥50%
OS PD-L1 ≥50%
KN-042

84. Mok, Lancet, 2019

85. PFS/OS fall-off faster
with single-agent anti-
PD-L1…Mok, Lancet, 2019

86. Combined CT + IO is a
standard of care in 1st-Line
NSCLC

87. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far

88. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far
You may decide NOT to
need one, any way

89. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far
You may decide NOT to
need one, any way
If CT + IO is your
choice…

90. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far
You may decide NOT to
need one, any way
If CT + IO is your
choice…
It is not a sin to give CT + IO
in PD-L1 negative…

91. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far

92. If you are considering
single-agent
pembrolizumab
Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far

93. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far
Not crazy, at all, with single
agent Pembro in
PD-L1 ≤ 50%
If you are considering single-
agent pembrolizumab

94. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far
Not crazy, at all, with single
agent Pembro in
PD-L1 ≤ 50%
Some patients may have died because
they did not receive chemo in single-
agent pembro trials
If you are considering single-
agent pembrolizumab

95. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Pembro is your drug,
PD-L1 is your biomarker…
so far
Single-agent Pembro an option
for strong PD-L1 expression…
who are not too sick
Not crazy, at all, with single
agent Pembro in
PD-L1 ≤ 50%
Some patients may have died because
they did not receive chemo in single-
agent pembro trials

96. Combined CT + IO is a
standard of care in 1st-Line
NSCLC

97. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Atezo is your drug,
Your biomarker will be
dictated by ROCHE…

98. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Atezo is your drug,
Your biomarker will be
dictated by ROCHE…
You may decide NOT to
need one, any way

99. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Atezo is your drug,
Your biomarker will be
dictated by ROCHE…
You may decide NOT to
need one, any way
Not even EGFR or ALK…

100. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Atezo is your drug,
Your biomarker will be
dictated by ROCHE…
You may decide NOT to
need one, any way
Not even EGFR or ALK…
I am not ready for that, though…

101. Combined CT + IO is a
standard of care in 1st-Line
NSCLC
If Atezo is your drug,
Your biomarker will be
dictated by ROCHE…
You may decide NOT to
need one, any way
Not even EGFR or ALK…
You don’t practice in
Colombia

102. 17.07.2019

103. @onconerd
Inspirado en: Michael Bierut, 2013, Logo para Mohawk Fine Papers