ESMO Preceptorship Programme, Immuno-Oncology, Singapore, 26-27 November 2018
Recent advances with ICPI: Results
in approved indication: advanced
non-small-cell lung cancerDr Ross Soo, MB BS, PhD, FRACP
Department Haematology-Oncology, National University Hospital
National University Cancer Institute, Singapore
National University Health System
Disclosures
• Advisory Board: Astra-Zeneca, BMS, Boehringer Ingelheim, Celgene, Ignyta, Lilly, Merck, Novartis, Pfizer, Roche, Taiho
• Research grant: Astra-Zeneca
Evolving ICI treatment in advanced NSCLC
2015
•FDA approval nivolumab in pre-Tx non-sq and sq NSCLC
2016
•FDA approval pembrolizumab in 1L Tx NSCLC PD-L1 50%+ w/o EGFR/ALK
•FDA approval pembrolizumab in pre-Tx NSCLC PD-L1 1%+
•FDA approval atezolizumab in pre-Tx NSCLC regardless PD-L1 status
2017
•FDA approval pembrolizumab + chemo in 1L Tx non-sq NSCLC
regardless PD-L1 status
•IMpower 150 data
2018
•FDA approval pembrolizumab + pem/ platinum in 1L Tx non-sq NSCLC w/o EGFR/ALK
•FDA approval pembrolizumab + chemo in 1L Tx sq NSCLC
•IMpower 130, 131, 132, 150, KN42, CM227 data
Outline: results in advanced NSCLC
2nd line
• PD-1 inhibitors
• CM-017 (Sq NSCLC)
• CM-057 (non Sq NSCLC)
• KN-010 (NSCLC)
• PD-L1 inhibitors
• OAK
• ARTIC
1st line
• Monotherapy ICI for non-Sq, Sq
• KN-024, KN-042
• Chemo + ICI
• Non-Sq: KN-189, IMpower150, 130, 132
• Squamous: KN-407, Impower131
• ICI + ICI
• CM227
• MYSTIC
CHECKMATE 057: non-Sq NSCLC
CHECKMATE 057: non-Sq NSCLC
Borghaei NEJM 2015, Horn ESMO Asia 2015
CHECKMATE 057: high PD-L1 expression is associated with
OS & PFS in non-SCC
Borghaei NEJM 2015
High PD-L1
expression
Low PD-L1
expression
Brahmer NEJM 2015
Nivolumab
n=135
Docetaxel
n=137
mOS mo
(95% CI)
9.2
(7.33,
12.62)
6.0
(5.29, 7.39)
# events 103 122
HR=0.62 (0.48, 0.81); P=0.0004
Docetaxel
18-month OS rate=13%
OS (
%)
Time (months)
0614253751576986113135 0Nivolumab
Number of Patients at Risk
047111722334669104137Docetaxel 1
Nivolumab18-month OS rate=28%
100
90
80
70
60
50
40
30
10
0
20
332724211815129630 30
RR: 20% vs 9%
Overall survival
Checkmate017
CHECKMATE 017: No association between tumor PD-L1
expression and OS or PFS
Brahmer NEJM 2015
KeyNote 010: Second-Line Pembrolizumab vs
Docetaxel in PD-L1+ Advanced NSCLC
Treatment
continued for 24
mos or until PD†
or unacceptable toxicity
*Corticosteroid premedication allowed. †Disease progression determined by radiological imaging. In the case of
investigator-assessed clinical disease progression, treatment permitted until confirmatory scan completed 4-6 wks later.
Stratified by ECOG PS, region,
and PD-L1 expression
Pts with advanced NSCLC
who progressed after
platinum-based chemotherapy
(and TKI if EGFR+ or ALK+); ≥ 1% PD-L1+ tumor cells;
ECOG PS 0-1
(N = 1034)
Pembrolizumab 2 mg/kg IV Q3W (n = 345)
Docetaxel* 75 mg/m2 IV Q3W (n = 343)
Pembrolizumab 10 mg/kg IV Q3W (n = 346)
Herbst et al. Lancet 2016; 387: 1540–50
• Randomized, open-label phase II/III study
− Primary endpoints: OS and PFS
− Secondary endpoints: ORR, DoR, safety
KEYNOTE-010: similar for both pembrolizumab groups in each TPS patient
population
Herbst, et al. Lancet 2015
2L+ Regimen Median OS, mo
HR(95% CI) p value
Pembro 2mg/kg14.9
0.54 (0.38, 0.77)
0.00024
Pembro 10mg/kg17.3
0.50(0.36, 0.7)
0.00002
Docetaxel 75mg/m2
8.2 – –
2L+ Regimen Median OS, mo
HR(95% CI) p value
Pembro 2mg/kg10.4
0.71(0.58, 0.88)
0.00076
Pembro 10mg/kg12.7
0.61(0.49, 0.75)
0.0001
Docetaxel 75mg/m2
8.5 – –
0
10
20
30
40
50
60
70
80
90
100O
ve
rall
su
rviv
al (
%)
Number at risk:
Pembro 2mg/kg 139 110 51 20 3 0
Pembro 10mg/kg 151 115 60 25 1 0
Docetaxel 75mg/m2 152 90 38 19 1 0
0
10
20
30
40
50
60
70
80
90
100
Ove
rall
su
rviv
al (
%)
Number at risk:
Pembro 2mg/kg 344 259 115 49 12 0
Pembro 10mg/kg 346 255 124 56 6 0
Docetaxel 75mg/m2 343 212 79 33 1 0
0 5 10 15 20 25Time (months)
0 5 10 15 20 25Time (months)
Pembro 2mg/kg
Pembro 10mg/kg
Docetaxel
Pembro 2mg/kg
Pembro 10mg/kg
Docetaxel
TPS ≥50% TPS ≥1%
OAK: Phase III atezolizumab vs docetaxel
OAK study: OS benefit with atezolizumab regardless of
PD-L1 status
ESMO Guidelines
Nivolumab is recommended in both squamous [I, A; ESMO-MBCS v1.1 score: 5] and
non-squamous NSCLC
[I, A; ESMO-MBCS v1.1 score: 5]
Pembrolizumab is recommended in patients with previously treated NSCLC with PD-L1
expression > 1%
[I, A; ESMO-MCBS v1.1 score: 5]
Atezolizumab is recommended in patients with advanced NSCLC previously treated
with one or two prior lines of ChT
[I, A; ESMO-MCBS v1.1 score: 5]
Outline: results in advanced NSCLC
2nd line
• PD-1 inhibitors
• CM-017 (Sq NSCLC)
• CM-057 (non Sq NSCLC)
• KN-010 (NSCLC)
• PD-L1 inhibitors
• OAK
• ARTIC
1st line
• Monotherapy ICI for non-Sq, Sq
• KN-024, KN-042
• Chemo + ICI
• Non-Sq: KN-189, IMpower150, 130, 132
• Squamous: KN-407, Impower131
• ICI + ICI
• CM227
• MYSTIC
KEYNOTE-024: Pembrolizumab versus chemotherapy in
first-line NSCLC
Reck M, et al. N Engl J Med 2016
KEYNOTE-024: Phase III, open-label, randomised study
• Key eligibility criteria included:
– stage IV NSCLC
– no previous systemic therapy for metastatic disease
– PD-L1 TPS ≥50%
– ECOG PS 0-1
– no activating EGFR mutations or ALK translocations
Stratified by: • ECOG status (0 vs 1)• Tumour histologic type (squamous v non-squamous)• Region (East Asia vs non-East Asia)
N=305
Pembrolizumab 200mg q3w for 35 cycles (N=154)
Platinum-doublet chemotherapy (4–6 cycles)* (N=151)
R
Primary endpointPFS (independent review)
Key secondary endpointsOS
ORR
Safety
1:1
*carboplatin plus pemetrexed, cisplatin plus pemetrexed, carboplatin plus gemcitabine, cisplatin plus gemcitabine, or carboplatin plus paclitaxel. Chemotherapy regimens that included
pemetrexed were permitted only for patients who had non-squamous tumours.
Pembrolizumab monotherapy is highly active in the 1st
line setting
PFS
HR 0.50 (95% CI, 0.37–0.68)
P<0.001
OS
HR 0.60 (95% CI, 0.41–0.89)
P=0.005
Pembrolizumab Chemotherapy
ORR: 44.8% 27.8%
Time to resp: 2.2m 2.2m
PFS: 10.3m 6.0m
Reck NEJM 2016.
Adverse events
Reck M, et al. N Engl J Med 2016.
1/2Grade
3/4
Pembrolizumab
Chemotherapy
Incid
ence (
%)
50
45
40
35
30
25
20
15
10
5
0
Lower frequency of adverse events with
pembolizumab vs chemotherapy
1st line pembrolizumab monotherapy is better than
chemotherapy in NSCLC TPS 50%+
OS
HR 0.60 (95% CI, 0.41–0.89)
P=0.005
Pembrolizumab Chemotherapy
ORR: 44.8% 27.8%
Time to resp: 2.2m 2.2m
PFS: 10.3m 6.0m
Reck NEJM 2016, Brahmer ASCO 2017
12
OS
Mos
OS
(%
)
100
80
60
40
20
0240 3 6 9 15 18 21
Pembro
(n = 154)
CT
(n = 151)
Median OS, mos NR 14.5
HR (95% CI) 0.63 (0.46-0.88); P = .003
Updated OS
Better OS if pembrolizumab was initiated 1st rather than
platinum-doublet
Is pembrolizumab effective at a lower PD-L1 cutoff?
KN042
KEYNOTE-042 Study Design
4Gilberto Lopes
aPemetrexed maintenance therapy was optional but strongly encouraged for patients with nonsquamous histology.
Key Eligibility Criteria
• Untreated locally advanced or metastatic NSCLC of any histology
• PD-L1 TPS ≥1%
• No sensitizing EGFR or ALK alterations
• ECOG PS 0 or 1
• No untreated or unstable CNS metastases
• No history of pneumonitis that required systemic corticosteroids
Pembrolizumab
200 mg Q3W
for up to 35 cycles
Carboplatin AUC 5 or 6 Q3W +
Paclitaxel 200 mg/m2 Q3Wa
ORCarboplatin AUC 5 or 6 Q3W +
Pemetrexed 500 mg/m2 Q3Wa
for up to 6 cycles
N = 637
N = 637
Stratification Factors• Region (east Asia vs rest of the world)
• ECOG PS (0 vs 1)
• Histology (squamous vs nonsquamous)• PD-L1 TPS (≥50% vs 1-49%)
End points
• Primary: OS in PD-L1 TPS ≥50%, ≥20%, and ≥1%
• Secondary: PFS and ORR in TPS ≥50%, ≥20%,
and ≥1%; safety in TPS ≥1%
Randomize 1:1
Slides courtesy of G. Lopes
0 6 1 2 1 8 2 4 3 0 3 6 4 2
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
M o n th s
OS
,
%
N o . a t R is k
4 1 3 3 0 5 2 5 1 1 4 4 7 3 2 4 2 0
4 0 5 3 1 3 2 1 0 1 0 6 5 3 1 4 1 0
Events HR (95% CI) P
Pembro 230 (55.7%) 0.77
(0.64-0.92)
0.0020
Chemo 266 (65.7%)
Median (95% CI)17.7 mo (15.3-22.1)
13.0 mo (11.6-15.3)
40.5%
29.6%
TPS >20%
0 6 1 2 1 8 2 4 3 0 3 6 4 2
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
M o n th s
OS
,
%
N o . a t R is k
6 3 7 4 6 3 3 6 5 2 1 4 1 1 2 3 5 2 0
6 3 7 4 8 5 3 1 6 1 6 6 8 8 2 4 1 0
Events HR (95% CI) P
Pembro 371 (58.2%) 0.81
(0.71-0.93)
0.0018
Chemo 438 (68.8%)
Median (95% CI)16.7 mo (13.9-19.7)
12.1 mo (11.3-13.3)
39.3%
28.0%
TPS >1%
0 6 1 2 1 8 2 4 3 0 3 6 4 2
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
M o n th s
OS
,
%
N o . a t R is k
2 9 9 2 2 4 1 8 9 1 0 7 5 9 2 2 2 0
3 0 0 2 3 1 1 4 9 7 5 4 0 1 1 1 0
Events HR (95% CI) P
Pembro 157 (52.5%) 0.69
(0.56-0.85)
0.0003
Chemo 199 (66.3%)
Median (95% CI)20.0 mo (15.4-24.9)
12.2 mo (10.4-14.2)
44.7%
30.1%
TPS >50%
0 6 1 2 1 8 2 4 3 0 3 6 4 2
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
M o n th s
OS
,
%
N o . a t R is k
3 3 8 2 3 9 1 7 6 1 0 7 5 3 1 3 0 0
3 3 7 2 5 4 1 6 7 9 1 4 8 1 3 0 0
Events HR (95% CI)
Pembro 214 (63.3%) 0.92
(0.77-1.11)Chemo 239 (70.9%)
Median (95% CI)13.4 mo (10.7-18.2)
12.1 mo (11.0-14.0)
34.6%
26.5%
TPS 1-49% (exploratory)
Overall survival: driven by high PD-L1 expression
Pembrolizumab is considered a standard first-line option for patients with advanced
NSCLC and PD-L1 expression 50% who do not have contraindications to use of
immunotherapy
[I, A; ESMO-MCBS v1.1 score: 5]
PD-L1 IHC should be systematically determined in advanced NSCLC [I, A]
Chemotherapy + Immune checkpoint inhibitor for
non-squamous NSCLC
• KN-189: pemetrexed/ Cb +/- pembro
• IMpower132: pemetrexed/ platinum +/- atezo
• IMpower150: paclitaxel/ Cb + atezo +/- bev
• IMpower130: nab paclitaxel/ Cb + atezo
Primary endpoint:
OS, PFS
Secondary:
ORR, DoR, safety
Chemo/pembro Chemotherapy
ORR: 47.6% 18.9%
DoR: 11.2m 7.8m
OS benefit regardless of PD-L1 status
Gandhi AACR 2018
Pembrolizumab in combination with pemetrexed
and a platinum-based ChT should be considered a
standard option in metastatic non-squamous NSCLC
[I, A; ESMO-MCBS v1.1 score: 4]
IMpower132
• Co-primary endpoints: INV-assessed PFS and OS
• Secondary endpoints: INV-assessed ORR and DOR, PRO and safety measures
• Exploratory analyses: clinical and biomarker subgroup analyses
• Biomarker-evaluable tissue not mandatory for enrolment (was available from 60% of patients)
Maintenance therapy
Arm PPa
Carboplatin or cisplatin+ pemetrexed
4 or 6 cycles
Pemetrexeda
Su
rviv
al
follo
w-u
p
Chemotherapy-naive patients with Stage IV non-squamous NSCLC
without EGFR or ALKgenetic alteration
Stratification factors:• Sex• Smoking status
• ECOG PS• Chemotherapy regimen
N = 578
R1:1
Arm APPa
Atezolizumab+ carboplatin or cisplatin
+ pemetrexed
4 or 6 cycles
Atezolizumaba
+ pemetrexeda Maintenance
Treatment until PD by
RECIST v1.1 or loss of
clinical benefit
Induction therapy
Papadimitrakopoulou WCLC 2018
Final Investigator-Assessed PFS, ORR and DOR
CR, complete response; DOR, duration of response; HR, hazard ratio; IRF, independent review facility; ORR, objective response rate; PR, partial response.
IRF-assessed median PFS was 7.2 mo with APP and 6.6 mo with PP (stratified HR: 0.758 [95% CI: 0.623, 0.923] P = 0.055)Data cutoff: May 22, 2018.
5.2 mo(95% CI: 4.3, 5.6)
7.6 mo(95% CI: 6.6, 8.5)
HR 0.60 (95% CI: 0.49, 0.72)P < 0.0001
Minimum follow-up, 11.7 mo
Median follow-up, 14.8 mo
APP PP
6-mo PFS 59.1% 40.9%
12-mo PFS 33.7% 17.0%
APP PP
ORR, % 47% 32%
CR 2% 1%
PR 45% 32%
Median DOR, mo 10.1 7.2
Ongoing response, %
42% 30%
Atezolizumab in combination with
pemetrexed and a platinum-based ChT is a
therapeutic option in metastatic non-
squamous NSCLC
[I, B]
IMpower 150
Socinski ASCO 2018
Cb/ paclitaxel/ bevacizumab/ atezo longer OS vs Cb/ paclitaxel/
bevacizumab
Socinski ASCO 2018
Cb/ paclitaxel/ bevacizumab/ atezo vs Cb/ paclitaxel/
bevacizumab
Socinski ASCO 2018
No OS benefit with Cb+ paclitaxel + atezo vs Cb+ paclitaxel +
bevacizumab
Socinski ASCO 2018
Combination of atezolizumab and
bevacizumab with carboplatin and paclitaxel
is a therapeutic option in patients with PS 0-1
with metastatic nonsquamous NSCLC, in the
absence of contraindications to use of
immunotherapy
[I, A]
IMpower130 study design
• Co-primary endpoints: investigator-assessed PFS and OS (ITT-WT population)
– ITT-WT population: randomised patients excluding those with EGFR or ALK genomic alterations
• Key secondary endpoints: OS and PFS (ITT population and by PD-L1 expression), ORR and safety
– ITT population could be formally tested for OS/PFS if ITT-WT OS was positive
Atezo 1200 mg IV q3w; carboplatin area under the curve 6 mg/mL/min q3w; nab-paclitaxel 100 mg/m2 IV q3w;
PD-L1 status tested with VENTANA SP142 IHC assay; data cut-off: 15 March 2018
*Crossover to receive atezo at PD was permitted only for patients enrolled to protocol versions 1–4 Cappuzzo, et al. ESMO 2018 (Abs LBA53)
Patients with
chemotherapy-naive stage
IV non-squamous NSCLC
Stratification:
• Sex
• Baseline liver
metastases
• PD-L1 tumour
expression
(ITT: N = 723;
ITT-WT: n = 679)
R
2:1
Atezo + carboplatin +
nab paclitaxel (CnP)
Carboplatin + nab
paclitaxel (CnP)*
Induction treatment
(4 or 6 21-day cycles)Maintenance treatment
Atezo
Best supportive care
or pemetrexed q3w
Treat until investigator-
assessed loss of clinical
benefit or toxicity
Treat until PD or toxicity
Su
rviv
al
foll
ow
-up
Median: 18.6 mo
(95% CI: 16.0, 21.2)
Median: 13.9 mo
(95% CI: 12.0, 18.7)
OS
(%
)
HR: 0.79(95% CI: 0.64, 0.98)
P = 0.033
IMpower130: OS (ITT-WT)
Cappuzzo, et al. ESMO 2018 (Abs LBA53)
OS (%) 1 year 2 years
Atezo + CnP 63.1% 39.6%
CnP 55.5% 30.0%
Combination therapy in squamous cell NSCLC
• KN407
• IMpower131
KN407
OS not influenced by PD-L1 expression
KN407
Combination of pembrolizumab and
carboplatin with paclitaxel or nab-P is a
standard choice in patients with metastatic
squamous NSCLC
[I, A]
IMpower131
Atezolizumab 1200 mg IV q3w; carboplatin AUC 6 IV q3w; nab-paclitaxel 100 mg/m2 IV qw; paclitaxel 200 mg/m2 IV q3w. a Patients with a sensitising EGFR mutation or ALK translocation must have disease progression or intolerance to treatment with ≥ 1 approved targeted therapies. Testing for EGFR mutation or ALK translocation was not mandatory.
Arm A
Atezolizumab +
Carboplatin + Paclitaxel
4 or 6 cycles
Atezolizumab
Arm C (control)
Carboplatin + Nab-Paclitaxel
4 or 6 cycles
Best Supportive
Care
Su
rviv
al
foll
ow
-up
Stage IV squamous NSCLC• Chemotherapy naivea
• ECOG PS 0 or 1
• Any PD-L1 IHC status
Stratification factors:
• Sex• PD-L1 IHC expression
• Liver metastases
N = 1021
R1:1:1
Arm B
Atezolizumab +
Carboplatin + Nab-Paclitaxel
4 or 6 cycles
Atezolizumab
Maintenance therapy (no crossover permitted)
Until PD per RECIST v1.1
or loss of clinical
benefit
Until PD per RECIST v1.1
Co-primary endpoints• Investigator-assessed PFS per RECIST v1.1 (ITT)
• OS (ITT)
Secondary endpoints• PFS and OS in PD-L1 subgroups
• ORR, DOR; safety
Jotte ASCO 2018
IMpower131
INV-Assessed PFS in the ITT Population (Arm B vs Arm C)
Data cutoff: January 22, 2018.
INV, investigator. a Stratified HR.
Minimum follow-up, 9.8 moMedian follow-up, 17.1 mo
Time (months)
12.0%
24.7%
12-month PFS
Arm B:Atezo + CnP
Arm C: CnP
Median PFS (95% CI), mo
6.3 (5.7, 7.1)
5.6 (5.5, 5.7)
HRa (95% CI)P value
0.71 (0.60, 0.85)0.0001
Pro
gre
ssio
n-F
ree
Su
rviv
al
(%)
No. at risk
Jotte ASCO 2018
Use of atezolizumab with carboplatin/nab-PC
today represents an option in patients with
metastatic squamous NSCLC
[I, B; not EMA-approved]
IO + IO combinations
• Checkmate 227
High TMB is associated with increased anti-tumor
response in a range of tumors
Nivolumab NSCLC (CM026)
RIZVI 2015, Carbone NEJM 2017, Hellmann Cancer Cell 2018
Pembrolizumab NSCLC
Nivolumab+ ipilimumab NSCLC (CM012)
100
75
50
25
0
0 3 6 9 12 15 18 21 24 27 30 33 36
1-y OS = 62.4%
1-y OS = 19.6%1-y OS = 23.4%
Months
Low TM B M ed TMB High TM B
Median OS
(95% CI), mo
3.4
(2.8, 7.3)
3.6
(1.8, 7.7)
22.0
(8.2, NR)
Nivolumab+ ipilimumab SCLC (CM032)
TMB v ORR in tumors
CM227: Nivo/ Ipi vs chemo in high TMB
Nivolumab + Ipilimumab
Chemo doublet
PD-L1 1+%N=1189
Nivolumab
Nivolumab + Ipilimumab
Chemo doublet
PD-L1 <1%N=550
Nivolumab
Nivolumab + Ipilimumab
N=139
Chemo doublet
N=160
Part 1 Endpoints:
Overall survival in PD-L1 selected
PFS (BICR) in TMB >10 regardless PD-L1
Advanced NSCLCEGFR/ ALK-ve
Hellman NEJM 2018
Longer PFS with nivolumab in patients with TMB
>10mt/Mb
PFS: 7.2 vs 5.5m
Nivo/ ipi in high TMB PFS benefit all subgroups
including histology, PD-L1 status
Hellman NEJM 2018
Nivo/ Ipi or chemo/ nivo in low PD-L1
Presented By Hossein Borghaei at 2018 ASCO Annual Meeting
PFS: Nivolumab + Chemotherapy vs Chemotherapy in Patients With <1% Tumor PD-L1 Expression
Presented By Hossein Borghaei at 2018 ASCO Annual Meeting
PFS: Nivolumab + Chemotherapy and Nivolumab + Ipilimumab <br />By TMB
Presented By Hossein Borghaei at 2018 ASCO Annual Meeting
Checkmate 227: TMB as a biomarker
• High TMB: 1st line Nivo/ ipi > chemo for PFS – regardless of PD-L1.
– durable PFS
• Low PD-L1– High TMB (> 10mt/ Mb): longer PFS with Ipi/ Nivo or chemo+ nivo vs chemo
– Low TMB: No PFS benefit with with either Ipi/ Nivo or chemo+ nivo
• TMB– Cost
– TAT
– Applicability across other NGS platforms• No standard platform/Lack of cross-platforms comparison
– different number of genes, cutoffs
– different variants within genes of interest
– different informatics pipelines
Nivolumab plus ipilimumab represents an optional
treatment regimen for patients with NSCLC with a
high TMB
[I, A]
D.Planchard et al, annals of onco 2018
IO first line
IO 2nd line
D.Planchard et al, annals of onco 2018
IO first line
IO 2nd line
2 year survival rate
66.3% v 55.6%
PACIFIC: Updated Safety Summary
APPROVALS ACROSS THE WORLD…
Indication: locally advanced, unresectable, no progression after platinum CT-RT
Regulatory Authority Stage Chemo-RT PD L1+
Canada Locally advanced, Unresectable Platinum – based CT-RT No
Australia Locally Advanced, Unresectable Platinum- based CT-RT No
Switzerland Locally advanced, Unresectable Definitive platinum – based CRT No
Japan Locally advanced, Unresectable Definitive chemoradiation No
US FDA Unresectable, III Concurrent platinum CT-RT No
EMA Locally advanced, Unresectable Platinum – based CT-RT PD L1 > 1%
Conclusion
• Pre-treated NSCLC– atezolizumab, nivolumab, and pembrolizumab are approved and is
superior to docetaxel
• 1st line setting EGFR/ ALK-ve NSCLC– Pembrolizumab monotherapy is superior to chemotherapy in high PD-L1
expression (TPS 50%+)
– Combination chemotherapy/ ICI is more effective than chemotherapy regardless PD-L1 status
– Combination chemotherapy/ ICI/ bevacizumab is more effective than chemotherapy/ bevacizumab
• TMB: promising, requires prospective validation
