Actualización para el año de 2018.

1. Biomarcadores de utilidad en inmno-
oncología de NSCLC
Mauricio Lema Medina MD
Clínica de oncología de Astorga / Clínica SOMA
Simposio ACHO
Bogotá,
Hotel Cosmos 100
27.04.2018

2. 2
Cuál de las
siguientes
NO es
verdad?
P R E G U N T A
Se define como TMB alto más
de 9 mutaciones por megabase
de ADN
1
La combinación PD-L1 <1% y
TMB alto se asocia a buena
respuesta a Nivo + Ipi en
primera línea
4
Aprox. 70% de los pacientes
con Pembro +/- quimio en
primera línea están vivos al año
3
Pembro + Quimio es superior a
Quimio en primera línea con
PD-L1 >1% escamocelular de
pulmón
2
El 66% de los pacientes con
NSCLC tienen TMB bajo.
5
La amplificación de la MDM2
se asocia a hiperprogresión
con anti PD1
6
Biomarcadores para inmunoterapia en cáncer del pulmón

3. @onconerd

4. Conflicts of interest for this lecture
Mauricio Lema
I have been paid for lectures by BMS, MSD,
Boehringer-Ingelheim, Novartis

5. Previously, on
BIOMARKERS

6. PD-L1
expression

7. PD-L1 expression in
NSCLC

8. Jassem, J, ESMO, 2017
Discordant in 34%

9. Anti-PD1 in 1st-
Line

10. Nivolum
ab
Chemothera
py
CheckMate-026: OS in Pts With ≥ 5% PD-L1
Nivolumab
(n = 211)
C
Median OS, mos
(95% CI)
14.4
(11.7-17.4)
1-yr OS rate, % 56.3
All randomized pts (≥ 1% PD-L1+) HR: 1.07 (95% CI: 0.86-
1.33)
HR: 1.02 (95% CI: 0.80-1.30)
▪ 60.4% in the chemotherapy
arm had subsequent
nivolumab therapy
▪ 43.6% in the nivolumab arm
had subsequent systemic
therapy
Socinski M, et al. ESMO 2016. Abstract LBA7_PR.
Mos
OS(%)
2421181512963 27
100
80
60
40
0
20
0 30
Slide credit: clinicaloptions.com
mNSCLC 1L PD-L1 ≽5%

11. 5% cut-off unable to select
patients likely to benefit from
single-agent nivolumab
CheckMate 26

12. High PD-L1 TPS

13. Pembrolizumab in NSCLC (KEYNOTE-001 Cohort):
OS by PD-L1 Expression
Pts at
Risk, n 119 92 56 22 5 4 3 0
161 119 58 15 6 4 0 0
76 55 33 8 0 0 0 0
100
80
60
40
20
0
0 4 8 12 16 20 24 28
OS(%)
Mos
PS 1-49%
PS < 1%
PS ≥ 50%
PS
Median OS,
Mos (95% CI)
≥ 50% NR (13.7-NR)
1-49% 8.8 (6.8-12.4)
< 1% 8.8 (5.5-12.0)
Garon EB, et al. N Engl J Med. 2015;372:2018-2028. Garon EB, et al. AACR 2015.
Abstract CT04. Slide credit: clinicaloptions.com

14. Reck M, et al. N Engl J Med. 2016;375:1823-1833.
Pem
(n =
Median PFS, mos 1
HR (95% CI)
KEYNOTE-024: PFS
0
10
20
30
40
50
60
70
80
90
100
0 3 6 9 12 15 18
10
4
89 44 22 3 115
4151 99 70 18 9 1 0
Mos
PFS(%)
Pts at Risk, n
62%
50% 48
%15%
Slide credit: clinicaloptions.com
mNSCLC 1L PD-L1 ≽50%

15. For the 30% with PD-L1 expression
≽50%, anti-PD1 (Pembrolizumab)
is indicated in 1L
-Level 1-
KEYNOTE 24

16. PD-L1 in second-
line

17. CheckMate 017: PFS by PD-L1 Expression Level
Brahmer J, et al. N Engl J Med. 2015;373:1627-1639. Slide credit: clinicaloptions.com

18. PD-L1 expression uninformative
when considering IO in
Squamous - NSCLC
CHECKMATE 17

19. CheckMate 057: OS by PD-L1 Expression
19
mOS, Mos
Nivo 17.7
Doc 9.0
mOS, Mos
Nivo 19.4
Doc 8.1
mOS, Mos
Nivo 19.9
Doc 8.0
mOS, Mos
Nivo 10.5
Doc 10.1
mOS, Mos
Nivo 9.8
Doc 10.1
mOS, Mos
Nivo 9.9
Doc 10.3
≥ 1% PD-L1 Expression
Level
Mos
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
OS(%)
Nivo
Doc
HR: 0.58 (95% CI: 0.43-0.79)
≥ 5% PD-L1 Expression Level
Mos
HR: 0.43 (95% CI: 0.30-0.62)
≥ 10% PD-L1 Expression Level
Mos
HR: 0.40 (95% CI: 0.27-0.58)
< 1% PD-L1 Expression Level
Mos
< 10% PD-L1 Expression Level
Mos
< 5% PD-L1 Expression Level
Mos
HR: 0.87 (95% CI: 0.63-1.19) HR: 0.96 (95% CI: 0.73-
1.27)
HR: 0.96 (95% CI: 0.74-1.25)
Borghaei H, et al. N Engl J Med. 2015;373:1627-
1639.
Nivo
Doc
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
OS(%)
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
100
90
80
70
60
50
40
30
10
0
20
3024211815129630 27
Slide credit: clinicaloptions.com

20. PD-L1
expression is
not the whole
story for Anti-
PD(L)1 therapy
in Non-
Squamous
NSCLC 2L
But, some
expression of
PD-L1 is
reassuring in
the context of
anti-PD(L)1
therapy in
Non-squamous
NSCLC 2L

21. BIOMARKERS 2018

22. Wang, H., Agulnik, J., Kasymjanova, G., Wang, A., Cohen, V., Small, D., … Spatz, A. (2018).
Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer. Annals of
Oncology. https://doi.org/10.1093/annonc/mdy126
blocks are suitable for immunohistochemical testing for PDL1

23. Wang, H., Agulnik, J., Kasymjanova, G., Wang, A., Cohen, V., Small, D., … Spatz, A. (2018).
Cytology cell blocks are suitable for immunohistochemical testing for PD-L1 in lung cancer. Annals of
Oncology. https://doi.org/10.1093/annonc/mdy126
blocks are suitable for immunohistochemical testing for PDL1
TPS <1% TPS 90%TPS 1-49%

24. The importance of PD-L1
expression when early anti PD-
(L)1 agents are integrated into
RT / Chemo in NSCLC

25. PACIFIC: Durvalumab after Chemoradiotherapy
in Stage III Non–Small-Cell Lung Cancer.
Hui, R., … Özgüroğlu, M. (2017). Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. New England Journal of Medici
Stage III unresectable
NSCLC
Non-progressors after
chemo-radiation
ECOG PS 0/1
No significant autoimmune
disease
No prior exposure to
immunotherapy
2:1
Durvalumab
10 mg/kg q2w, up to 1 yr
Placebo
q2w, up to 1 yr
Endpoints: Coprimary endpoints PFS and OS

26. PACIFIC: Durvalumab after Chemoradiotherapy in
Stage III Non–Small-Cell Lung Cancer.
Hui, R., … Özgüroğlu, M. (2017). Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. New England Journal of Medici

27. PACIFIC: Durvalumab after Chemoradiotherapy in
Stage III Non–Small-Cell Lung Cancer.
Hui, R., … Özgüroğlu, M. (2017). Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. New England Journal of Medici

28. PACIFIC: Durvalumab after Chemoradiotherapy in
Stage III Non–Small-Cell Lung Cancer.
Hui, R., … Özgüroğlu, M. (2017). Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. New England Journal of Medici

29. KeyNote 189 - Pembrolizumab plus
Chemotherapy in Metastatic Non–Small-Cell
Lung Cancer
Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Canc
Metastatic nonsquamous NSCLC
No sensitizing EGFR or ALKmutations
Treatment-naive for metastatic NSCLC
ECOG PS 0/1
Measurable disease
Tumor sample for PD-L1 status available
No CNS metastasis symptoms
No significant autoimmune
disease/treatment
2:1
Stratification
Smoking history
By PD-L1 expression (<1% vs ≥1%)
Cisplatin vs Carboplatin
Pembrolizumab + Pemetrexed
+ Platin
Pemetrexed + Platin
Endpoints: Coprimary endpoints OS / PFS (by central review)

30. KeyNote 189 -
Pembrolizumab plus
Chemotherapy in
Metastatic Non–
Small-Cell Lung
Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S.,
Esteban, E., Felip, E., De Angelis, F., … Garassino,
M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New
England Journ

31. 31
KeyNote 189
P D - L 1 e x p r e s s i o n i n
<1% - 31%
1-49% - 31%
≥50% - 32%
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ

32. KeyNote 189 - Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer
Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Canc

33. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ

34. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ

35. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ
PD-L1 <1% PD-L1 1-49%
PD-L1 ≥50%

36. 36
61.
71.
73.
52. 51.
48.
KeyNote 189
C h e m o + P e m b r o l i z u m a b i n m e t a s t a t i c N S C L C
1 2 - m o n t h O S i n P e m b r o l i z u m a b + C h e m o v s C h e m o
61%
52%
71%
51%
73%
48%
PD-L1 TPS <1% PD-L1 TPS 1-49% PD-L1 TPS ≥50%%
Pembro + Chemotherapy Chemotherapy
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ

37. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ
Overall Response Rate (by TPS)

38. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ
PFS

39. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ
In conclusion, in patients with metastatic nonsquamous
NSCLC without sensitizing EGFR or ALK mutations, the
addition of pembrolizumab to induction therapy with
pemetrexed and a platinum-based drug and to pemetrexed
maintenance therapy resulted in significantly longer overall
survival and progression-free survival and a higher response
rate than the addition of placebo at a cost of a low incidence of
renal dysfunction at the first interim analysis. The survival
benefit for pembrolizumab-combination therapy was observed
across all categories of PD-L1 expression.

40. KeyNote 189 - Pembrolizumab plus Chemotherapy in Metastatic
Non–Small-Cell Lung Cancer
Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., … Garassino, M. C. (2018). Pembrolizumab plus Chemotherapy in
Metastatic Non–Small-Cell Lung Cancer. New England Journ
In conclusion, in patients with metastatic nonsquamous
NSCLC without sensitizing EGFR or ALK mutations, the
addition of pembrolizumab to induction therapy with
pemetrexed and a platinum-based drug and to pemetrexed
maintenance therapy resulted in significantly longer overall
survival and progression-free survival and a higher response
rate than the addition of placebo at a cost of a low incidence of
renal dysfunction at the first interim analysis. The survival
benefit for pembrolizumab-combination therapy was observed
across all categories of PD-L1 expression.

41. The TMB story

42. Tumor Mutational Burden and Response Rate to PD-1 Inhibition
Yarchoan, NEJM, 2017

43. Tumor Mutational Burden and Response Rate to PD-1 Inhibition
Yarchoan, NEJM, 2017
Our linear correlation formula — objective response
rate=10.8×loge(X)−0.7, where “X” is the number of
coding somatic mutations per megabase of DNA

44. CheckMate 227: Nivolumab plus Ipilimumab
in Lung Cancer with a High Tumor
Mutational Burden
Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/N
Untreated metastatic squamous
and Non-squamous NSCLC
No untreated brain metastasis.
No drug sensitive EGFR/ALK
mutations
No autoimmune disease
PD-L1 ≥1%
Nivolumab + Ipilimumab
Platinum doublet
Nivolumab
Stratification: Squamous vs Non-squamous
R
Untreated metastatic squamous
and Non-squamous NSCLC
No untreated brain metastasis.
No drug sensitive EGFR/ALK
mutations
No autoimmune disease
PD-L1 <1%
Nivolumab + Ipilimumab
Platinum doublet +
Nivolumab
Platinum doublet
Stratification: Squamous vs Non-squamous
R
Endpoints:
High TMB: PFS Nivo + Ipi vs Chemo
PD-L1≥1%: OS Nivo + Ipi vs Chemo

45. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946
Nivo + Ipi Arm
Nivolumab: 3 mg/kg q2w
Ipilimumab: 1 mg/kg q6w
Nivolumab Arm
Nivolumab: 240mg q2w
Nivo + Chemo Arm
Nivolumab: 360mg q3w
Platinum doublet

46. CheckMate 227: Nivolumab plus Ipilimumab
in Lung Cancer with a High Tumor
Mutational Burden
Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/N
1004 patients with evaluable TMB
444 patients with at least 10 mutations / MB by FoundationOne
High TMB (44.2%)
139 assigned to Nivo + Ipilimumab 160 assigned to Chemotherapy

47. CheckMate 227 - Part 1:
Nivolumab plus Ipilimumab
in Lung Cancer with a High
Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A.,
Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden.
https://doi.org/10.1056/NEJMoa1801946.
https://doi.org/10.1056/NEJMOA1801946

48. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946

49. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946

50. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946

51. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946
In Low TMB:
PFS Nivo + Ipi: 3.2 mo
PFS Chemo: 5.5 mo

52. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946

53. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946

54. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946

55. CheckMate 227 - Part 1: Nivolumab plus Ipilimumab in
Lung Cancer with a High Tumor Mutational Burden
Hellmann, M. D., Ciuleanu, T.-E., Pluzanski, A., Lee, J. S., Otterson, G. A., Audigier-Valette, C., … Paz-Ares, L. (2018). Nivolumab plus Ipilimumab in Lung
Cancer with a High Tumor Mutational Burden. https://doi.org/10.1056/NEJMoa1801946. https://doi.org/10.1056/NEJMOA1801946
Among patients with a high tumor
mutational burden, the benefit of
nivolumab plus ipilimumab over
chemotherapy was similar in patients
with a PD-L1 expression level of at
least 1% and those with a level of
less than 1%.

56. Combination biomarker selection for 1st line NSCLC
TMB
high
TMB
low
PD-L1
high
PD-L1
low
PD-L1
high
PD-L1
low
Pembrolizumab Nivolumab + Ipilimumab Pembrolizumab Chemotherapy
Rivzy, AACR, Chicago, 2018

57. Developing stories…

58. 10/13/2014 11/17/2014
Pembrolizumab
Hyperprogression associated with MDM2 amplification
Kato, S. Clin Cancer Res 2017.

59. https://www.ncbi.nlm.nih.gov/pubmed/28351930/
Percent change from baseline imaging among 4 patients with MDM2 amplification whose tumors progressed rapidly while
on immunotherapy
Kato, S. Clin Cancer Res 2017.

61. 61
Cuál de las
siguientes
NO es
verdad?
P R E G U N T A
Se define como TMB alto más
de 9 mutaciones por megabase
de ADN
1
La combinación PD-L1 <1% y
TMB alto se asocia a buena
respuesta a Nivo + Ipi en
primera línea
4
Aprox. 70% de los pacientes
con Pembro +/- quimio en
primera línea están vivos al año
3
Pembro + Quimio es superior a
Quimio en primera línea con
PD-L1 >1% escamocelular de
pulmón
2
El 66% de los pacientes con
NSCLC tienen TMB bajo.
5
La amplificación de la MDM2
se asocia a hiperprogresión
con anti PD1
6
Biomarcadores para inmunoterapia en cáncer del pulmón

62. 62
Last remarks
T h e B I O M A R K E R S f o r I . O . a g e n t s i n N S C L C c o n t i n u e t o
e v o l v e
P D - L 1 e x p r e s s i o n i n f i r s t - l i n e
High PD-L1 TPS associated with a better
outcome with single-agent IO
Patients with Lower PD-L1 may still benefit from
early integration of IO agents, in combination

63. 63
Last remarks
T h e B I O M A R K E R S f o r I . O . a g e n t s i n N S C L C c o n t i n u e t o
e v o l v e
P D - L 1 e x p r e s s i o n i n s e c o n d - l i n e
PD-L1 expression irrelevant for
Squamous-NSCLC
Some PD-L1 expression required for
anti PD1 in Non Squamous

64. 64
Last remarks
T h e B I O M A R K E R S f o r I . O . a g e n t s i n N S C L C c o n t i n u e t o
e v o l v e
P D - L 1 e x p r e s s i o n p o s t c h e m o / R T
No clear signal.
Poor biomarker in this setting

65. 65
Last remarks
T h e B I O M A R K E R S f o r I . O . a g e n t s i n N S C L C c o n t i n u e t o
e v o l v e
T M B
High TMB is like High PD-L1 TPS
Low TMB is Like low PD-L1 TPS
Some low PD-L1 TPS have high TMB: these
may benefit from early integration of I.O.

66. 66
Last remarks
T h e B I O M A R K E R S f o r I . O . a g e n t s i n N S C L C c o n t i n u e t o
e v o l v e
T M B
High TMB is like High PD-L1 TPS
Low TMB is Like low PD-L1 TPS
Some low PD-L1 TPS have high TMB: these
may benefit from early integration of I.O.

67. 67
Last remarks
T h e B I O M A R K E R S f o r I . O . a g e n t s i n N S C L C c o n t i n u e t o
e v o l v e
P D - L 1 e x p r e s s i o n i n f i r s t - l i n e
High PD-L1 TPS associated with a better outcome
with single-agent IO
Patients with Lower PD-L1 may still benefit from early
integration of IO agents, in combination
T M B
High TMB is like High PD-L1 TPS
Low TMB is Like low PD-L1 TPS
Some low PD-L1 TPS have high TMB: these may
benefit from early integration of I.O.
P D - L 1 e x p r e s s i o n i n s e c o n d - l i n e
PD-L1 expression irrelevant for Squamous-NSCLC
Some PD-L1 expression required for anti PD1 in Non
Squamous
P D - L 1 e x p r e s s i o n p o s t C h e m o / R T
No clear signal.
Poor biomarker in this setting
T M B