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Inmunoterapia en cáncer de pulmón
Manuel Cobo Dols
Oncología Médica
Hospital R.U. Málaga regional y Virgen de la Victoria
Madrid 6-04-2017
Anti PD1/PDL1 Nivolumab Pembrolizumab Atezolizumab Durvalumab Avelumab
Anti CTL4 Ipilimumab Tremelimumab
Combinación *Terapia clásicas Quimioterapia Radioterapia *Nuevas dianas *Nuevos inmunomoduladores
Contexto * 2º línea CPNM * 1º línea CPNM * Adyuvancia * Estadio III con RT * En Mutaciones (EGFR/ALK..) * Microcitico * Escamoso * Adenocarcinoma
Anti PD1/PDL1 Con biomarcador Sin biomarcador Con PDL1 Sin PDL1 Puntos de corte PDL1 Otros biomarcadores
Combinaciones - Variaciones - Permutaciones
Inmunoterapia Cáncer pulmón
Anti-PDL1/PD1 therapies in advanced NSCLC
*And approved therapy for EGFR Mut+ or ALK+ NSCLC §Tumour proportion score (TPS) ≥50%, where TPS is the proportion of viable tumour cells showing partial or complete membrane PD-L1 expression ¶Study data available
Nivolumab Pembrolizumab Atezolizumab Durvalumab
Company Bristol-Myers Squibb Merck Roche AstraZeneca
Brand name Opdivo Keytruda – –
Target PD-1 PD-1 PD-L1 PD-L1
Class mAb (IgG4) mAb (IgG4) mAb (IgG1) mAb (IgG1)
Dosing 3mg/kg q2w 2mg/kg q3w 1200mg q3w 20mg/kg q4w
Administration Intravenous infusion Intravenous infusion Intravenous infusion Intravenous infusion
Indications
/approvals in
NSCLC
US/EU: metastatic
NSCLC after prior
CT*
US: PD-L1+§
metastatic NSCLC
after prior CT*
Not yet approved Not yet approved
Pivotal trials in ≥2L
NSCLC
CheckMate 017¶,
CheckMate 057¶ KEYNOTE-010¶ POPLAR¶, OAK
Pivotal trials in 1L
NSCLC
CheckMate 026
CheckMate 227
KEYNOTE-024
KEYNOTE-042
KEYNOTE-189
IMpower 110, IMpower 111,
IMpower 130, IMpower 131,
IMpower 132, IMpower 150
NEPTUNE
MYSTIC
Diagnostic assay 28-8 22C3 SP142 SP263
of PD-L1 expression in advanced NSCLC Nivolumab Pembrolizumab Atezolizumab Durvalumab
Detection antibody 28-81 22C31 SP1422 SP2633
IHC platform Dako1 Dako1 Ventana1 Ventana3
Cell types scored
for NSCLC TC1 TC1 IC and TC1,2 TC1
Cut-off definitions
for NSCLC
PD-L1+ as ≥5% of
TCs exhibiting
positive membrane
PD-L1 staining at
any intensity
PD-L1+ as ≥50% of
viable TCs showing
partial or complete
membrane PD-L1
expression*
TC3 or IC3: ≥50% of TCs or ≥10% of ICs
TC2/3 or IC2/3: ≥5% of TCs or ICs
TC1/2/3 or IC1/2/3: ≥1% of TCs or ICs
TC0 and IC0: <1% of TCs and ICs
(Proportion of cells stained at any
intensity)
PD-L1+ as ≥25% of
TCs with
membrane PD-L1
staining
Estimated PD-L1
prevalence in
NSCLC ~46%1
~25%1 37%*
68%*
16%*
~48%4
*For the 22C3 assay, the proportion of viable tumour cells showing partial or complete membrane PD-L1 staining is termed the tumour proportion score (TPS) 1. Kerr, et al. J Thorac Oncol 2015; 2. Vansteenkiste, et al. ECC 2015; 3.Rebelatto, et al. ASCO 2015; 4. Rizvi, et al. ASCO 2015
7
PFS by Tumor Mutation Burden Tertile CheckMate 026 TMB Analysis: Nivolumab in First-line NSCLC
100
90
80
70
60
50
40
30
20
10
0
0 3 6 9 12
Months
15 18 21 24
PF
S (
%)
High
Low
Medium
Medium
n = 49 n = 47
3.6
(2.7, 6.9)
Low
n = 62
4.2
(1.5, 5.6)
9.7
(5.1, NR)
Median PFS, months
(95% CI)
High
Nivolumab Arm Chemotherapy Arm
Medium
n = 53 n = 60
6.5
(4.3, 8.6)
Low
n = 41
6.9
(5.4, NR)
5.8
(4.2, 8.5)
Median PFS, months
(95% CI)
High 100
90
80
70
60
50
40
30
20
10
0
0 3 6 9 12
Months
15 18
High
Low
Medium
21
• Data for patients with low and medium TMB were pooled in subsequent analyses
Carbone. IASLC 2015
Pt CD8+ Density, Invasive Margin Before Treatment
Predicted Probability of Response
Blinded Prediction Clinical Response (RECIST 1.1)
1 58 0.35 Progression Progression
2 159 0.37 Progression Progression
3 329 0.40 Progression Progression
4 341 0.41 Progression Progression
5 2120 0.75 Response Stable
6 5466 0.98 Response Progression
7 2211 0.76 Response Response
8 3810 0.92 Response Response
9 4294 0.95 Response Response
10 4948 0.97 Response Response
11 5565 0.98 Response Response
12 6004 0.99 Response Response
13 5951 0.99 Response Complete response
14 7230 0.99 Response Complete response
15 6320 0.99 Response Complete response
Lo ideal:la densidad de infiltración de LT8 junto con expresión de PD-L1
P. C. Tumeh et al., Nature 2014; 515,:568 -71.
La densidad de LT CD8 en el margen de invasión del tumor fue mucho más predictiva de beneficio a Pembrolizumab
que PD-L1. .- Este dato sugiere que expresión de PD-L1 en el tumor es más poderoso como biomarcador cuando se
observa en el contexto de una respuesta de cel T activos.
Rationale for Combination strategies
• Tumors can present as either immunogenic or nonimmunogenic
• Immune system priming or depletion of immunosuppressive factors through combination therapies can boost tumor immunogenicity, and therefore, susceptibility to I-O therapy
10
CD=cluster of differentiation; I-O=immuno-oncology; PD-L1=programmed death ligand 1. Adapted from Sharma P, Allison JP. Science. 2015;348(6230):56-61.
Nonimmunogenic tumor
Immunogenic tumor
CD8 T cell
CD4 T cell
CD4 T cell
CD8 T cell
CD8 T cell expressing
CD45RO
CD8 T cell expressing
PD-L1 CD8 T cell
with granzyme B
Tumor cell expressing
PD-L1
PRIMING
Immunosuppressive factors ▼
CPNCP avanzado. 2º línea
Checkmate 017 and 057: Nivolumab vs docetaxel Kaplan-Meier Estimates of OS
Nivolumab (n=135)
Docetaxel (n=137)
Events, n (%) 110 (81) 128 (93)
Median OS, mo (95% CI)
9.2 (7.3, 12.6)
6.0 (5.1, 7.3)
HR (95% CI) 0.62 (0.47, 0.80)
Nivolumab (n=292)
Docetaxel (n=290)
Events, n (%) 228 (78) 247 (85)
Median OS, mo (95% CI)
12.2 (9.7, 15.1)
9.5 (8.1, 10.7)
HR (95% CI) 0.75 (0.63, 0.91)
Checkmate 057 (non-SQ NSCLC)
Nivolumab
Docetaxel
Number of patients at risk: Nivolumab Docetaxel
100
80
60
40
20
0 0 3 6
128 89
Time (Months)
21 30 33 39 O
S (%
) 18 9 12 24 27 36
292 290
233 243
194 194
97 53
18 6
6 3
0 0
112 66
171 150
148 111
81 45
46 25
0 1
15
2-yr OS=16%
Δ13%
2-yr OS=29%
1-yr OS=51%
Δ12%
1-yr OS=39%
Checkmate 017 (SQ NSCLC)
100
80
60
40
20
0 0 3 6
51 22
Time (Months)
21 30 33 39
OS
(%)
18 9 12 24 27 36
135 137
113 104
86 69
34 14
14 6
7 4
0 0
38 17
69 46
57 33
29 11
19 9
1 1
15
Number of patients at risk: Nivolumab Docetaxel
2-yr OS=23%
2-yr OS=8%
Δ15%
1-yr OS=42%
1-yr OS=24%
Δ18%
Based on February 2016 DBL. Symbols refer to censored observations. Minimum follow-up for survival: 24.2 months. Borghaei H et al. Poster presentation at ASCO 2016. 9025.
12
Nivolumab
Docetaxel
Bhramer J, et al. NEJM 2015 Borghaei H et al. NEJM Sept 2015
NO ESCAMOSOS ESCAMOSOS
Bhramer J, et al. NEJM 2015
ESCAMOSOS
Borghaei H et al. NEJM Sept 2015
Overall survival at the 1%, 5% and 10% PD-L1 expression levels
NO ESCAMOSOS
Checkmate 057. EMA. Global de los pacientes
Presentation Number: Presentation Title – Presenting Author
3-Month Landmark Analysis of OS CheckMate 057: Nivolumab vs Docetaxel in Previously Treated NSQ NSCLC
17
Nivo (n = 232)
Doc (n = 244)
Median OS, mo
17.4 11.3
Events, n 131 179
HR (95% CI)
0.59 (0.47, 0.74)
Alive at 3 Months −
All Patients ITT Population1
Nivo (n = 292)
Doc (n = 290)
Median OS, mo
12.2 9.4
Events, n 190 223
HR (96% CI)
0.73 (0.59, 0.89)
Based on a March 18, 2015 database lock 1. Borghaei H, et al. N Engl J Med 2015;373:1627–1639.
Nivolumab
Docetaxel
OS
(%
)
Months
100
90
80
70
60
50
40
30
10
0
20
27 21 18 15 12 9 6 3 0 24
Months
100
90
80
70
60
50
40
30
10
0
20
27 21 18 15 12 9 6 3 0 24
Nivo (n = 82)
Doc (n = 87)
Median OS, mo
14.7 11.4
Events, n 51 62
HR (95% CI)
0.66 (0.45, 0.97)
Alive at 3 Months –
Patients With <1% PD-L1 Expression
Months
100
90
80
70
60
50
40
30
10
0
20
27 21 18 15 12 9 6 3 0 24
Garón et al NEJM 2015
Pembrolizumab
Herbst. Lancet 2015
Herbst. Lancet 2015
Herbst. Lancet 2015
POPLAR: randomised all-comer phase II study
*Archival or new tissue required for pre-dose testing
• Primary analysis conducted with 173 events, minimum follow-up 13 months • Interim analysis with 153 events and minimum follow-up 10 months was presented at ASCO
2015 (Spira et al. Abstract 8010)
Fehrenbacher, et al. Lancet 2016
• Metastatic or locally
advanced NSCLC (2L/3L)
• Disease progression on a
prior platinum therapy
• N=287
Primary endpoint:
• OS in ITT and PD-L1
expression subgroups
Additional endpoints:
• Estimate PFS, ORR and
DOR in ITT and PD-L1
expression subgroups
• Evaluate safety
Key inclusion criteria
Docetaxel
75mg/m2 IV q3w
until disease
progression
Atezolizumab
1200mg IV q3w
until loss of clinical
benefit R
1:1
Patients stratified by:
• PD-L1 IC expression (0 vs 1 vs 2 vs 3)*
• Histology (squamous vs non-squamous)
• Prior chemotherapy regimens (1 vs 2)
Endpoints
24
ASCO 2016
25
POPLAR: OS by PD-L1 expression
*Stratified HR; Data cut-off May 8, 2015
HR* = 0.49 (0.22, 1.07)
P value = 0.068
n = 47
Median 15.5 mo
(9.8, NE)
Median 11.1 mo
(6.7, 14.4)
HR* = 0.54 (0.33, 0.89)
P value = 0.014
n = 105
Median 15.1 mo
(8.4, NE) Median 7.4 mo
(6.0, 12.5)
HR* = 0.59 (0.40, 0.85)
P value = 0.005
n = 195
Median 15.5 mo
(11.0, NE) Median 9.2 mo
(7.3, 12.8)
HR* = 1.04 (0.62, 1.75)
P value = 0.871
n = 92
Median 9.7 mo
(6.7, 12.0)
Median 9.7 mo
(8.6, 12.0)
Atezolizumab
Docetaxel
Censored +
Fehrenbacher, et al. Lancet 2016
Phase III OAK study design
• Barlesi et al, Atezolizumab Phase III OAK Study. Lancet 207
Atezolizumab 1200 mg IV q3w
PD or loss of clinical benefit
Docetaxel 75 mg/m2 q3w
Locally Advanced or
Metastatic NSCLC
•1–2 prior lines of chemo
including at least 1 platinum
based
•Any PD-L1 status
N = 1,225 enrolleda
PD
R
1:1
Stratification factors
•PD-L1 expression
•Histology
•Prior chemotherapy
regimens
Primary Endpoints (first 850 enrolled patients):
•OS in the ITT population
•OS in patients with patients with PD-L1 expression on ≥ 1% TC or IC
Secondary Endpoints: ORR, PFS, DoR, Safety aA prespecified analysis of the first 850 patients provided sufficient power to test the co-primary
endpoints of OS in the ITT and TC1/2/3 or IC1/2/3 subgroup (≥ 1% PD-L1 expression).
TC, tumor cells; IC, tumor-infiltrating immune cells.
(n = 850)
aStratified HR for ITT and TC1/2/3 or IC1/2/3. Unstratified HR for other subgroups. TC, tumor cells; IC, tumor-infiltrating immune cells; OS, overall survival. Barlesi et al. ESMO 2016 LBA44
Overall survival, ITT (n = 850) and PD-L1 subgroups
Atezolizumab
Docetaxel
Median 9.6 mo
(95% CI, 8.6, 11.2)
Median 13.8 mo
(95% CI, 11.8, 15.7)
Ove
rall
Su
rviv
al (%
)
Months
HR, 0.73a
(95% CI, 0.62,
0.87)
P = 0.0003 Minimum follow up = 19 months
425 363
30
5 248 218 188 157 74 28 1
425 336 26
3
195 151 123 98 51 16 0
No. at risk
Atezolizumab
Docetaxel
0.2 2
Subgroup
TC1/2/3 or IC1/2/3a
TC0 and IC0
ITTa
TC3 or IC3
TC2/3 or IC2/3
Median OS, mo
n = 425 n = 425
9.6
8.9
10.3
10.8
8.9
13.8
12.6
15.7
16.3
20.5 0.41
0.67
0.74
0.75
0.73
0.2 1
2
In favor of
docetaxel
Hazard Ratioa
In favor of
atezolizumab
Docetaxel Atezolizumab
OS HR
• Barlesi et al, Atezolizumab Phase III OAK Study. Lancet 207
OS, PD-L1 EXPRESSION ON ≥ 50% TC or ≥ 10% IC
TC3 or IC3; 16% of patients
Median 8.9 mo
(95% CI, 5.6, 11.6) Median 20.5 mo
(95% CI, 17.5, NE)
HR, 0.41a
(95% CI, 0.27, 0.64)
P < 0.0001b
Months
Ove
rall
Su
rviv
al (%
)
Atezolizumab
Docetaxel
Minimum follow up = 19 months
• Barlesi et al, Atezolizumab Phase III OAK Study. Lancet 207
Atezolizumab
Docetaxel
Months
HR, 0.75a
(95% CI, 0.59, 0.96)
P = 0.0205b
Median 8.9 mo
(95% CI, 7.7, 11.5)
Median 12.6 mo
(95% CI, 9.6, 15.2)
OS, PD-L1 Expression ON < 1% TC AND IC TC0 and IC0; 45% of patients
Ove
rall
Su
rviv
al (%
) Minimum follow up = 19 months
• Barlesi et al, Atezolizumab Phase III OAK Study. Lancet 207
CA209-003: Nivo Monotherapy in NSCLC1
Time Since First Dose (months)
100
80
60
0
40
20
0 6 12 18 30 24 36 42 48 54 66 60
3-year OS=18% 2-year OS=24% O
S (
%)
1-year OS=42%
Checkmate 017: Squamous NSCLC2
OS
(%
)
100
80
60
40
0
20
33 27 24 21 18 15 12 9 6 3 0 30
Docetaxel
2-yr OS =23%
2-yr OS=8% Nivolumab
Time (months)
Checkmate 057: Non-squamous NSCLC2
Time (months) 27 18 15 9 6 21 12 3 0 24 30
100
80
60
40
0
20
OS
(%)
Docetaxel
2-yr OS=29%
2-yr OS=16% Nivolumab
OS
(%
)
18-mo OS=40%
100
80
60
40
20
0 0 3 6 9 12 15 18 21 24 27
Atezolizumab
Docetaxel
18-mo OS=27%
Time (months)
OAK: NSCLC3
18-mo OS=37% 18-mo OS=43% 18-mo OS=24%
Checkmate 032: SCLC5
Time (months)
OS
(%
)
27 21 18 15 12 9 6 3 0 24 0
20
40
60
100
80 Nivolumab-3 Nivolumab-1/ipilimumab-3 Nivolumab-3/ipilimumab-1
1-year OS=33% 1-year OS=43% 1-year OS=35%
KN-010: ≥1% PD-L1 NSCLC4
Pembro 2 mg/kg
Docetaxel Pembro 10 mg/kg
0 5 Time (months)
OS
(%)
0
20
40
60
80
100
10 15 20 25 30
OS plateau demonstrates long-term benefit in 2L+ lung cancer with PD1/PDL1 therapy
Nivolumab is currently not approved for SCLC. 1. Gettinger SN. J Clin Oncol. 2015;33(18):2004-2012. 2. Borghaei H et al. Poster presentation at ASCO 2016. 9025. 3. Barlesi F et al. Oral presentation at ESMO 2016. LBA44. 4. Herbst RS et al. Poster presentation at ESMO 2016. LBA48. 5. Antonia SJ et al. Oral presentation at ASCO 2016. 100.
Meta-análisis Expresión PD-L1 en Ca pulmón pretratados
Passiglia F. Oncotarget 2016. PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis
- - PD-L1 no se puede definir como un biomarcador clásico.
- - Expresión de PD-L1 se correlaciona con densidad eficaz
de LTc (CD8) específicos contra el inmunopeptidoma
clonal del tumor. (Se puede usar como modelo predictivo
indirecto de eficacia a inmunoterapia).
- - Expresión de PD-L1 tiene aún muchas limitaciones: - - heterogeneidad en espacio – tiempo - y tipo de tratamiento previo
- - El modelo predictivo es diferente según las diferentes neoplasias
- - Limitación tecnológica por los diferentes Ac inmunohistoquímica.
- - Expresión de PD-L1 puede ser una herramienta para
disminuir la incertidumbre respecto a la estrategia
terapéutica más adecuada en cada momento : - - PD-L1 bajo: trat anti PD1 / PD-L1 pueden ser menos eficaces que
trat clásicos.
- - PD-L1 bajo: trat anti PD1 / PD-L1 + otros trat para aumentar el
“estatus inflamado” del tumor
Valor PDL1 en cáncer de pulmón
39% (1 CR, 6 PR)
CPNCP avanzado. 1º línea Monoterapia
PEMBROLIZUMAB
Reck M, et al. NEJM 2016
Reck M, et al. NEJM 2016
Reck M, et al. NEJM 2016
6
Phase 3 CheckMate 026 Study Design:
Nivolumab vs Chemotherapy in First-line NSCLC
Primary endpoint: PFS (≥5% PD-L1+)d
Secondary endpoints:
• PFS (≥1% PD-L1+)d
• OS
• ORRd
Nivolumab3 mg/kg IV Q2W
n = 271
Randomize 1:1
Key eligibility criteria:
• Stage IV or recurrent NSCLC
• No prior systemic therapy for
advanced disease
• No EGFR/ALK mutations sensitive to
available targeted inhibitor therapy
• ≥1% PD-L1 expressiona
• CNS metastases permitted if
adequately treated at least 2 weeks
prior to randomization
Chemotherapy (histology dependent)b
Maximum of 6 cycles
n = 270
Disease progression or
unacceptable toxicity
Disease
progression
Crossover
nivolumabc
(optional)
Tumor scans Q6W until
wk 48 then Q12W
aDako 28-8 validated; archival tumor samples obtained ≤6 months before enrollment were permitted; PD-L1 testing was centralizedbSquamous: gemcitabine 1250 mg/m2 + cisplatin 75 mg/m2; gemcitabine 1000 mg/m2 + carboplatin AUC 5; paclitaxel 200 mg/m2 + carboplatin AUC 6;
Non-squamous: pemetrexed 500 mg/m2 + cisplatin 75 mg/m2; pemetrexed 500 mg/m2 + carboplatin AUC 6; option for pemetrexed maintenance therapycPermitted if crossover eligibility criteria met, including progression confirmed by independent radiology reviewdTumor response assessment for PFS and ORR per RECIST v1.1 as determined by independent central review
Stratification factors at randomization:
• PD-L1 expression (<5% vs ≥5%)a
• Histology (squamous vs non-squamous)
Socinski M et al. Oral presentation at ESMO 2016
Checkmate 026: PD-L1> 5%
42
Nivolumab
Chemotherapy
Months
PFS
(%
)
24 21 18 15 12 9 6 3 27
100
80
60
40
0
20
0
All randomized patients (≥1% PD-L1+) HR = 1.17 (95% CI: 0.95, 1.43)
HR = 1.15 (95% CI: 0.91, 1.45), P = 0.2511
Months O
S (%
)
24 21 18 15 12 9 6 3 30
100
80
60
40
0
20
0 27
Nivolumab
Chemotherapy
HR = 1.02 (95% CI: 0.80, 1.30)
All randomized patients (≥1% PD-L1+) HR = 1.07 (95% CI: 0.86, 1.33)
CI=confidence interval; HR=hazard ratio; mos=months; OS=overall survival; PFS=progression-free survival; PD-L1=programmed death ligand 1. .
Nivolumab n = 211
Chemo n = 212
Median PFS, mos (95% CI)
4.2 (3.0, 5.6)
5.9 (5.4, 6.9)
1-year PFS rate, % 23.6 23.2
Nivolumab
n = 211
Chemo
n = 212
Median OS, mos
(95% CI)
14.4
(11.7, 17.4)
13.2
(10.7, 17.1)
1-year OS rate,
% 56.3 53.6
No. of patients at risk:
Nivo 211 104 71 49 35 24 6 3 1 0
Chem
o
212 144 74 47 28 21 8 1 0 0
No. of patients at risk:
Nivo 211 186 156 133 118 98 49 14 4 0 0
Chemo 212 186 153 137 112 91 50 15 3 1 0
Socinski M et al. Oral presentation at ESMO 2016
CheckMate 026: PFS and OS Subgroup Analyses
(All Randomized Patients)
CheckMate 026 vs. Keynote 024
Keynote 024 CheckMate 026
Tumor biopsy After metastatic diagnosis
Within 6 months
PD-L1 cut off 50% (22C3 clone) 5% (28-8 clone)
Prevalence 30% 50%
Imaging interval Q 9 weeks Q 6 weeks for first 48 weeks
Primary endpoint PFS (RECIST) PFS (IRRC)
Never smokers (PD-1) 3% 11%
Squamous histology 19% 24%
Time from diagnosis to treatment
? 2 months
Prior radiation ? 1 37.6 %
Socinski et al, ESMO 2016
Reck et al, ESMO 2016, NEJM 2016
Until loss of clinical benefit
Atezolizumab BIRCH: study design
1L = first line; 2L = second line; 3L = third line; DOR = duration of response; ECOG = Eastern Cooperative Oncology Group
IHC = immunohistochemistry; INV = investigator; IRF = Independent Review Facility; IV = intravenous; ORR = objective response rate
OS = overall survival; PD = progressive disease; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors
Cohort 1 (1L) No prior chemo
n=142
Cohort 2 (2L) 1 prior platinum chemo
n=271
Cohort 3 (≥3L) ≥2 prior chemos (including 1 platinum)
n=254
PD
Atezolizumab dosed at 1200 mg IV q3w in all cohorts.
• Locally advanced or
metastatic NSCLC
• Tumour PD-L1
expression by IHC (TC2/3
and/or IC2/3)
• ECOG PS 0 or 1
• No brain mets
N=667
• Primary endpoint: IRF-assessed ORR per RECIST v1.1
• Secondary endpoints: – IRF-assessed PFS, DOR per RECIST v1.1
– INV-assessed ORR, PFS, DOR per RECIST v1.1 and modified RECIST
– OS
– Safety
Besse, et al. ECC 2015
Garassino et al., WCLC 2016
Overall Survival
NE, not estimable.
TC3 or IC3 = TC ≥ 50% or IC ≥ 10% PD-L1–expressing cells;
TC2 and IC2 = ≥ 5% but IC < 10% and TC < 50% PD-L1–expressing cells;
TC2/3 or IC2/3 = TC or IC ≥ 5% PD-L1–expressing cells, respectively.
Data cutoff date: August 1, 2016.
Median duration of survival follow-up = 22.5 months
TC2/3 or IC2/3
(n = 138)
mOS (95% CI) 23.5 mo (18.1, NE)
12-mo OS rate (95% CI) 66.4% (58.1, 74.6)
TC3 or IC3
(n = 65)
mOS (95% CI) 26.9 mo (12.0, NE)
12-mo OS rate (95% CI) 61.5% (49.0, 74.0)
TC2 and IC2
(n = 73)
mOS (95% CI) 23.5 mo (18.1, NE)
12-mo OS rate (95% CI) 70.7% (59.8, 81.6)
EGFR mOS (95% CI)
Mutant 26.0 mo (20.1, 26.0)
Wild-type 20.1 mo (15.5, NE)
KRAS mOS (95% CI)
Mutant 24.1 mo (20.3, NE)
Wild-type 23.5 mo (15.5, NE)
Atezolizumab BIRCH: OS. No prior chemo
Median duration of survival follow-up = 22.5 months
TC2/3 or IC2/3
(n = 138)
mOS (95% CI) 23.5 mo
(18.1, NE)
12-mo OS rate
(95% CI)
66.4% (58.1,
74.6)
TC3 or IC3
(n = 65)
mOS (95% CI) 26.9 mo
(12.0, NE)
12-mo OS rate
(95% CI)
61.5% (49.0,
74.0)
TC2 and IC2
(n = 73)
mOS (95% CI) 23.5 mo
(18.1, NE)
12-mo OS rate
(95% CI)
70.7% (59.8,
81.6)
ATLANTIC (NCT02087423) is a Phase 2, open-label, single-arm trial
*PD-L1 expression levels assessed by immunohistochemistry (VENTANA PD-L1 [SP263] Assay); †ORR by independent central review (RECIST v1.1)
CT, chemotherapy; DCR, disease control rate; DoR, duration of response
Primary endpoint:
• ORR†
Secondary
endpoints:
• DoR, PFS, DCR,
OS
• Safety
• PK
• Immunogenicity
Durvalumab i.v. 10 mg/kg q2w up
to 12 months
• NSCLC patients
(Stage IIIB/IV)
• ≥2 prior systemic
treatment regimens
including 1 platinum-
based CT
• Recent (≤3 months)
tumour biopsy and
archived tumour tissue
block for PD-L1 testing
N=1980 screened
Cohort 1 (n=111)
EGFR mutation/ALK alteration
PD-L1 high (≥25% tumour cells)
Cohort 2 (n=265)
EGFR/ALK wild-type
PD-L1 high (≥25% tumour cells)
and PD-L1 low/negative
Cohort 3 (n=68)
EGFR/ALK wild-type
PD-L1 high (≥90% tumour cells)
Protocol
amendment
restricted
selection to
pts with PD-L1
high tumours*
Cohorts were independent;
Cohorts 2 and 3 enrolled sequentially
Garassino et. al IASLC 2016
Overall survival in Cohorts 2 and 3 (full analysis set)
*Median follow up for OS was 9.4 months (PD-L1 ≥25%); 9.3 months (PD-L1 <25%); and 7.0 months (PD-L1 ≥90%)
NC, not calculated; NR, not reached
No. of patients at risk:
PD-L1 ≥25% 149 127 97 79 66 47 14 3 1 1 0
PD-L1 <25% 94 75 56 48 32 24 16 1 0 0 0
No. of patients at risk:
PD-L1 ≥90% 67 53 39 19 7 0
1.0
0
Pro
port
ion a
live
0.8
0.6
0.4
0.2
0
3 6 9 30 12 15 18 21 24 27
1-year OS
47.7% (39.3–55.5)
34.5% (25.0–44.1)
1-year OS
50.8 (36.9–63.2)
Time from first dose (months)
1.0
0
Pro
port
ion a
live
0.8
0.6
0.4
0.2
0
3 6 9 12 15
Time from first dose (months)
Cohort 2 Cohort 3
Median OS (95% CI)*
PD-L1 ≥90% (n=67): NR (5.9–NC)
Median OS (95% CI)*
PD-L1 ≥25% (n=149): 10.9 (8.6–13.6)
PD-L1 <25% (n=94): 9.3 (5.9–10.8)
Garassino et. al IASLC 2016
Study design: First-line NSCLC cohort
Patients: key eligibility
criteria
• Histologically confirmed
stage IV or recurrent
NSCLC
• ECOG PS 0–1 and
estimated life expectancy ≥3
months
• No prior treatment for
metastatic or recurrent
NSCLC
• No activating EGFR
mutation or ALK
translocation
• Unselected for PD-L1
expression
Dosing
Avelumab
10 mg/kg (1h
IV) Q2W
until
confirmed
progression,
unacceptable
toxicity, or
withdrawal
Select assessments*
Best overall
response
by RECIST v1.1
Safety and
tolerability
Progression-free
survival
PD-L1 expression
* Radiological examinations performed every 6 weeks
Time to/duration of response and PFS (n=156)
Median PFS:
17.6 weeks (95% CI: 11.6, 23.6)
PFS rate at 24 weeks:
37.2% (95% CI: 28.6, 45.7)
• 28/35 patients (80%) responded by the 1st or 2nd assessment
• Response was ongoing in 24/35 (68.6%) at data cut-off
Presentation Number: Presentation Title – Presenting Author
Phase 1 CheckMate 012 Study Design: First-Line Nivolumab ± Ipilimumab in NSCLC
• Updated datad presented here are based on median follow-up durations of 22 months (monotherapy) and 16 months (combination cohorts)
– Overall additional follow-up relative to previous reports: monotherapy, +~18 months;1 combination cohorts, +6 months2
Primary endpoint: safety and tolerability
Secondary endpoints: ORR (RECIST v1.1) and PFS rate at 24 weeks assessed by investigators
Exploratory endpoints: OS, efficacy by PD-L1 expression
Stage IIIB/IV NSCLC (any histology), no prior chemotherapy for advanced disease, ECOG PS 0 or 1
Nivolumab 3 mg/kg IV Q2Wa Nivolumab 3 mg/kg IV Q2W
+ Ipilimumab 1 mg/kg IV Q12Wb
Nivolumab 3 mg/kg IV Q2W +
Ipilimumab 1 mg/kg IV Q6Wb
Until disease progressionc or unacceptable toxicity
ClinicalTrials.gov number NCT01454102; aTreatment allocation not randomized; bTreatment allocation randomized; earlier cohorts evaluated other dosing schedules/regimens2 cPatients tolerating study treatment permitted to continue treatment beyond RECIST v1.1-defined progression if considered to be deriving clinical benefit dBased on a September 2016 database lock 1. Gettinger S, et al. J Clin Oncol 2016;34:2980–2987; 2. Hellmann MD, et al. Lancet Oncol 2016 Dec 5. [Epub ahead of print].
51
Nivo 1 + Ipi 1 Q3W
(n = 31)
Nivo 1 Q2W + Ipi 1 Q6W
(n = 40)
Nivo 3 Q2W + Ipi 1 Q12W
(n = 38)
Nivo 3 Q2W + Ipi 1 Q6W
(n = 39) Nivo 3 Q2Wa
(n = 52)
Confirmed ORR, % (95% CI) 13
(4, 30) 25
(13, 41) 39
(24, 57) 31
(17, 48) 23
(13, 37)
Confirmed DCR, % (95% CI) 55 (36, 73) 58 (41, 73) 74 (57, 87) 51 (35, 68) 50 (36, 64)
Best overall response, %
Complete response Partial response
Unconfirmed partial response
0 13 3
0 25 3
0 39 5
0 31 8
8 15 0
Stable disease Progressive disease Unable to determine
42 35 6
33 30 10
34 13 8
21 26 15
27 38 12
PFS rate at 24 wks, % (95% CI) 55 (36, 71) NC 63 (44, 76) NC 41 (27, 54)
Median PFS, mos (95% CI) 10.6 (2.1, 16.3) 4.9 (2.8, ) 8.0 (4.2, ) 8.3 (2.6, ) 3.6 (2.3, 6.6)
Median OS, mos (95% CI) NR (11.5, ) NR (8.9, ) NR NR (8.7, ) 22.6 (14.9, )
Median length of follow-up, mos (range)
16.6 (1.8–24.5)
6.2 (0.4–13.1)
8.4 (0.9–12.3)
7.7 (1.1–12.2)
14.3 (0.2–30.1)
Summary of Efficacy
52 NR: the time point at which the percent of survivors drops below 50% has not been reached due to insufficient number of events and/or follow up. aResults for Nivo 3 Q2W are reported based on a March 2015 DBL
• Median DOR was not reached in any arm
• Unconventional immune-related responses were observed in arms Nivo 3 Q2W + Ipi 1 Q12W (n = 2), Nivo 3 Q2W + Ipi 1 Q6W (n = 1) and Nivo 3 Q2W (n = 3)
. Gettinger S, et al. J Clin Oncol 2016;34:2980–2987; 2. Hellmann MD, et al. Lancet Oncol 2016
Presentation Number: Presentation Title – Presenting Author
• 5 CRs (10%) were achieved in the nivolumab monotherapy cohort (1 in a patient with tumor PD-L1 expression <1%)
• 6 CRs (8%) were achieved in the nivolumab + ipilimumab cohortsa (3 in patients with tumor PD-L1 expression <1%)
43
21
57
92
23
13
28
50
0
20
40
60
80
100
Overall <1%
≥1%
≥50%
Nivo 3 + ipi 1 Q6/12W Nivo 3
Nivolumab ± Ipilimumab ORR by Tumor PD-L1 Expression
CheckMate 012: First-Line Nivolumab ± Ipilimumab in NSCLC
53
OR
R (
%)
Overall <1% ≥1% ≥50%
PD-L1 expression
n 52 77 16 19 32 46 12 13
Based on a September 2016 database lock; a3 determined radiographically per RECIST v1.1 and 3 identified by pathologic evaluation
Nivo 3 Q2W + Ipi 1 Q6/12W Nivo 3 Q2W
. Gettinger S, et al. J Clin Oncol 2016;34:2980–2987; 2. Hellmann MD, et al. Lancet Oncol 2016
Presentation Number: Presentation Title – Presenting Author
OS by Tumor PD-L1 Expression CheckMate 012: First-Line Nivolumab ± Ipilimumab in NSCLC
54
Based on a September 2016 database lock
All treated patients (n = 77) ≥1% PD-L1 (n = 46) ≥50% PD-L1 (n = 13)
1-year OS rate: 76%
100
80
60
40
20
0
OS
(%
)
0 6 12 18 24 30 36 42 48
100
80
60
40
20
0
0 6 12 18 24 30 36 42 48
1-year OS rate: 87%
100
80
60
40
20
0
0 6 12 18 24 30 36 42 48
1-year OS rate: 100%
Nivo 3 Q2W +
ipi 1 Q6/12W
1-year OS rate: 73%
100
80
60
40
20
0
Months
OS
(%
)
0 6 12 18 24 30 36 42 48
100
80
60
40
20
0
Months
0 6 12 18 24 30 36 42 48
1-year OS rate: 69%
100
80
60
40
20
0
Months
0 6 12 18 24 30 36 42 48
1-year OS rate: 83%
All treated patients (n = 52) ≥1% PD-L1 (n = 32) ≥50% PD-L1 (n = 12)
Nivo 3 Q2W
• Data are based on median follow-up durations of 16 months (combination cohorts) and 22 months (monotherapy) . Gettinger S, et al. J Clin Oncol 2016;34:2980–2987; 2. Hellmann MD, et al. Lancet Oncol 2016
Presentation Number: Presentation Title – Presenting Author
55
Key eligibility criteria:
• Stage IV or recurrent NSCLC
• No prior systemic therapy for
advanced disease
• No EGFR/ALK mutations
sensitive to available targeted
inhibitor therapy
• CNS metastases permitted if
adequately treated ≥2 weeks
prior to randomization
Stratification factor at
randomization:
• Histology (squamous vs
non-squamous)
Randomize 1:1:1
Disease progression
or unacceptable
toxicity
PD-L1+
(≥1%)
PD-L1‒
(<1%)
Tumor
scans Q6W
until
week 48
then Q12W
Nivolumab monotherapy
240 mg Q2W
Nivolumab 3 mg/kg Q2W +
Ipilimumab 1 mg/kg Q6W
Chemotherapy
Nivolumab 360 mg Q3W + Chemotherapy
Nivolumab 3 mg/kg Q2W +
Ipilimumab 1 mg/kg Q6W
Chemotherapy
Phase 3 CheckMate 227 (NCT02477826) Study Design
. Gettinger S, et al. J Clin Oncol 2016;34:2980–2987; 2. Hellmann MD, et al. Lancet Oncol 2016
* PD-L1 positivity defined as ≥25% of tumor cells with membrane staining as determined by the Ventana PD-L1 IHC assay. Combination of durvalumab and tremelimumab is currently not approved for advanced/metastatic NSCLC. 1. Clinicaltrials.gov. NCT02542293. Accessed September 08, 2016. 2. Mok T et al. Poster presentation at ESMO Asia 2015. 480TiP.
NEPTUNE: Study Design1,2
Phase III, open-label, global study of durvalumab in combination with tremelimumab vs Pt-based chemotherapy in first-line treatment of advanced or metastatic NSCLC
• Primary Endpoint: OS
• Secondary Endpoints: OS, PFS, ORR, DOR, APF12, PFS2, PK,
immunogenicity, safety
N=800
Key Inclusion Criteria
• Treatment-naïve
• Evidence of Stage IV NSCLC
• No activating EGFR or ALK rearrangement
• PD-L1 positive* or negative
• ECOG PS 0 or 1
• No mixed SCLC or NSCLC NOS
• No brain metastases/spinal cord compression unless asymptomatic, treated, and stable
• No active or prior documented inflammatory bowel disease
Durvalumab 20 mg/kg Q4W + tremelimumab 1 mg/kg Q4W
n=400
SOC Pt-based doublet chemotherapy
Carboplatin + paclitaxel
NSQ: Carboplatin/cisplatin + pemetrexed SQ: Carboplatin/cisplatin + gemcitabine
n=400
R
MYSTIC: Study Design1,2
Phase III, open-label, first-line therapy study of durvalumab ± tremelimumab vs SOC in NSCLC
• Primary Endpoints: OS, PFS (combination vs SOC)
• Secondary Endpoints: PFS (combination vs SOC, mono vs SOC); HRQoL (combo
or mono vs SOC); PK (combo and mono); immunogenicity; ORR (combo vs SOC);
ORR & OS (mono vs SOC)
• Other: Safety and tolerability
Durvalumab 20 mg/kg Q4W + tremelimumab 1 mg/kg Q4W
Platinum-doublet chemotherapy Paclitaxel + carboplatin Pemetrexed + cisplatin or carboplatin Gemcitabine + cisplatin or carboplatin
Key Inclusion Criteria
• Treatment-naïve
• Evidence of Stage IV NSCLC
• No activating EGFR or ALK rearrangement
• ECOG PS ≤1
• No mixed SCLC or NSCLC NOS
• No prior immunomodulatory therapy
• No brain metastases/spinal cord compression unless asymptomatic, treated, and stable
• No active or prior documented inflammatory bowel disease
N=1092
R
1:1:1
Combination of durvalumab and tremelimumab is currently not approved for advanced/metastatic NSCLC. 1. Clinicaltrials.gov. NCT02453282. Accessed September 08, 2016. 2. Peters S et al. Poster presented at ELCC 2016.191TiP.
Durvalumab 20 mg/kg Q4W
CPNCP avanzado. 1º línea Combinación con QT
KEYNOTE-021—Cohort G: study design
Phase 2 study of pembrolizumab plus carboplatin and pemetrexed vs.
carboplatin and pemetrexed in first-line patients with non-squamous NSCLC
aRandomisation was stratified by PD-L1 TPS <1% and ≥1%.bIndefinite maintenance therapy with pemetrexed 500 mg/m2 Q3W permitted.
cClinically stable patients who were considered to be deriving clinical benefit by the investigator despite radiological evidence of disease progression could continue therapy until
progression was confirmed on imaging done at least 4 weeks later
AUC: area under the curve; ALK: anaplastic lymphoma kinase; DOR: duration of response; ECOG: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth
factor receptor; ILD: interstitial lung disease; NSCLC: non-small-cell lung cancer; ORR: objective response rate; OS: overall survival; PFS: progression-free survival; PD: progressive
disease; PD-L1: programmed death ligand 1; Q3W: every 3 weeks; RECIST: Response Evaluation Criteria In Solid Tumors; TPS: tumour proportion score.
Langer CJ, et al. Lancet Oncol 2016; http://dx.doi.org/10.1016/S1470-2045(16)30498-3.
Langer et al. Lancet Oncol 2016
KEYNOTE-021—Cohort G: progression-free survivala
ITT population
Analysis cut-off date: 08 August 2016.aRECIST v1.1 by blinded, independent central review.
CI: confidence interval; HR: hazard ratio; ITT: intention-to-treat; NR: not reached; PFS: progression-free survival; RECIST: Response Evaluation Criteria In Solid Tumors.
Langer CJ, et al. Lancet Oncol 2016; http://dx.doi.org/10.1016/S1470-2045(16)30498-3.
Langer et al. Lancet Oncol 2016
Analysis cut-off date: 08 August 2016. aNominal p value. CI: confidence interval; HR: hazard ratio; NR: not reached; OS: overall survival.
1. Langer CJ, et al. Lancet Oncol 2016; http://dx.doi.org/10.1016/S1470-2045(16)30498-3; 2. Langer CJ, et al. ESMO 2016 presentation.
Langer et al. Lancet Oncol 2016
Keynote 021. Overall Survivall
KEYNOTE-021—Cohort G: exposure and adverse event summary
As-treated populationa
Analysis cut-off date: 08 August 2016 aDefined as all patients who received at least one dose of the assigned study treatment AE: adverse event; IQR: interquartile
range.Langer CJ et al. Lancet Oncol 2016; http://dx.doi.org/10.1016/S1470-2045(16)30498-3.
Pembrolizumab +
chemotherapy
(n=59)
Chemotherapy
alone
(n=62)
Median duration of
treatment
(IQR)
8.0 months
(4.7–11.2)
4.9 months
(2.1–7.4)
Treatment-related AEs,
% Any grade Grade 3–5 Any grade Grade 3–5
Any 54 39 65 26
Serious 3 24 2 8
Leading to
discontinuation 2 8 8 5
Leading to death 0 2 0 3
Langer et al. Lancet Oncol 2016
Rizvi NA et al. J Clin Oncol. 2016;24(25):2969-2979.
Checkmate 012: PFS and OS, nivo + chemo
• Checkmate 012 represents the most mature data set evaluating anti–PD-1 + chemotherapy
• OS rates observed at 1 year were not maintained at 2 years
100
80
60
40
20
0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42
Time Since First Dose (months)
OS
(%)
Group Median OS,
months (range) 1-Year OS, %
2-Year OS, %
Nivo 10 mg/kg + Gem-Cis 11.6 (4.5–33.3) 50 25
Nivo 10 mg/kg + Pem-Cis 19.2 (7.6–35.1+) 87 33
Nivo 10 mg/kg + Pac-Carb 14.9 (3.2–34.2+) 60 27
Nivo 5 mg/kg + Pac-Carb NR (8.8–30.1+) 86 62
Group Median PFS,
months (range) 24-Week PFS, %
Nivo 10 mg/kg + Gem-Cis 5.7 (0.02+–14.1) 51
Nivo 10 mg/kg + Pem-Cis 6.8 (0.9+–24.6+) 71
Nivo 10 mg/kg + Pac-Carb 4.8 (0.7–28.7+) 38
Nivo 5 mg/kg + Pac-Carb 7.1 (0.02+–24.8+) 51
20
0 3 6 9 12 15 18 21 24 27 30
Time Since First Dose (months)
PFS
(%
)
40
60
80
100
0
Nivo 10 mg/kg + Gem-Cis Nivo 10 mg/kg + Pem-Cis Nivo 10 mg/kg + Pac-Carb Nivo 5 mg/kg + Pac-Carb
Nivo 10 mg/kg + Gem-Cis Nivo 10 mg/kg + Pem-Cis Nivo 10 mg/kg + Pac-Carb Nivo 5 mg/kg + Pac-Carb
GP28328: a phase Ib study of first-line atezolizumab plus chemotherapy in NSCLC
DLTs = dose-limiting toxicities; DOR = duration of response; IV = intravenous; 3w= every 3 weeks ORR = objective response rate PFS = progression-free survival NCT01633970
• Locally advanced or metastatic
NSCLC
• Histologically or cytologically
confirmed stage IIIB or IV disease
• ECOG PS 0–1
• No prior chemotherapy for
advanced disease
Atezolizumab IV q3w + carboplatin q3w + pemetrexed q3w
(n≤25)
Atezolizumab IV q3w + carboplatin q3w + paclitaxel q3w
(n≤25)
Atezolizumab IV q3w + carboplatin q3w + nab-paclitaxel q1w
(n≤25)
Endpoints • Safety (including DLTs)
Secondary endpoints • Pharmacokinetics • Best overall response • ORR • DOR • PFS
Loss of clinical benefit
Camidge, et al. WCLC 2015; Giaccone, et al. ECC 2015
Camidge DR et al. WCLC 2015
Summary of ongoing phase III studies with in NSCLC
Phase III 1L in non-squamous NSCLC
Atezolizumab + carbo/pac ± bev Combo
Phase III 1L in non-squamous NSCLC
Atezolizumab + carbo/nab-pac Combo
Phase III 1L in squamous NSCLC
Atezolizumab + carbo/pac or carbo/nab-pac Combo
Combo Phase III 1L in non-squamous NSCLC
Atezolizumab + carbo or cis/pem
CPNCP local / localmente avanzado
71
Alliance Foundation Trial (AFT-16)
Chemoradiation in Stage III Unresectable NSCLC
*Chemo/RT= carboplatin (AUC2) + paclitaxel 50 mg/m2 IV weekly x6 cycles +60 Gy qd x 30fxn § Consolidation chemotherapy = carboplatin AUC6 + paclitaxel 200 mg/m2 IV q21 days x 2 cycels
ORR=objective response rate; PD=progressive disease; RT=radiotherapy; QoL=quality of life
Phase II/III trial of induction immunotherapy with atezolizumab for patients with unresectable stage IIIA
and IIIB NSCLC eligible for chemoradiotherapy with curative intent and whose tumors express PD-L1
Phase III Objectives and Endpoints:
1. Primary endpoint: OS
2. Secondary endpoint: PFS, safety, QoL
Chemo/RT + Consolidation Adjuvant Immunotherapy
Chemo/RT +
Conoslidation
4 total cycles of
Atezolizumab induction
Alliance Standard
Chemo/RT* regimen
Alliance Standard Chemo
Consolidation§
Atezolizumab
1200mg q3w for 1
year
NSCLC
Stage
IIIA &
IIIB
PDL1+
Primary Endpoints: ORR following induction, PFS following induction + chemo/RT
R A
N D
O M
I Z
E
2:1
Atezolizumab
1200 mg IV
q3w
x4 cycles
Induction
Immunotherapy
Study Design & Endpoints NEOADJUVANT NIVOLUMAB IN NSCLC
Newly diagnosed resectable
stage I (>2cm)/II/IIIA NSCLC
Nivolumab 3mg/kg IV on
Day-28 & Day-14
Surgical resection on Day 0
Standard of care postoperative
treatment
Safety follow up for 30 days after
surgery
TUMOR
BIOPSY
BLOOD
DRAWS
VIABLE TUMOR
TILS
LYMPH NODE
CELLS
BLOOD DRAW
Ongoing Adjuvant PD-1/PD-L1 trials
CPNCP avanzado. Mutaciones
FUTURO
Greil et al. Cell Communication and Signaling (2017) 15:5
Dentro del complejo mundo inmuno-oncologico, necesitaremos biomarcadores que nos orienten a decidir cuáles de todos los nuevos fármacos será eficaz
IASLC 2016
Ann Oncol 2016
Inmunoterapia Cáncer pulmón. PREGUNTAS Con respecto a inmunoterapia con antiPD1/PDL1 en segunda línea de CPNCP, cuál de las siguientes preguntas es Verdadera 1.- El fármaco de elección es Nivolumab frente a los otros dos, pembrolizumab y atezolizumab 2.- la inmunohistoquímica con PD-L1 tiene demasiados inconvenientes clínicos y no se aconseja realizar para tomar una decisión de la mejor terapia a administrar 3.- Para la indicación de pembrolizumab en segunda línea, sólo se deberían considerar los que tienen un porcentaje de PD-L1 en inmunohistoquímica > 50% 4.- El Anticuerpo de inmunohistoquímica de PD-L1 asociado a atezolizumab es: el test de Ventana SP 142, y considera tanto células tumorales como inflamatorias.
Inmunoterapia Cáncer pulmón. PREGUNTAS Con respecto a inmunoterapia con antiPD1/PDL1 en primera línea de CPNCP, cuál de las siguientes preguntas es Verdadera 1.- Los pacientes con mutación de EGFR tienen el mismo beneficio que los pacientes WT para la inmunoterapia, porque suelen tener más expresión de PD-L1 2.- El único fármaco recomendado por las agencias regulatorias en primera línea, es Pembrolizumab en monoterapia cuando la expresión de PD-L1 > 50% 3.- La combinación de un anti PD1/PD-L1 + antiCTL4 sería la opción más recomendable en primera línea en paciente con alta expresión en inmunohistoquímica de PD-L1 4.- El beneficio de nivolumab en monoterapia frente a quimioterapia en primera línea de CPNM en paciente con nivel de expresión de PD-L1 > 50%, fue similar al del ensayo con pembrolizumab