ESMO 2018 CONGRESS
Transcript of ESMO 2018 CONGRESS
Supported by Eli Lilly and Company.
Eli Lilly and Company has not influenced the content of this publication
Developed in association with theEuropean Thoracic Oncology Platform
19–23 October 2018
Munich, Germany
ESMO 2018 CONGRESS
Letter from Prof Rolf Stahel
Dear Colleagues
It is my pleasure to present this ETOP slide set which has been designed to highlight and
summarise key findings in thoracic cancers from the major congresses in 2018. This slide
set specifically focuses on the ESMO 2018 Congress and is available in 4 languages –
English, French, Chinese and Japanese.
The area of clinical research in oncology is a challenging and ever changing environment.
Within this environment, we all value access to scientific data and research which helps to
educate and inspire further advancements in our roles as scientists, clinicians and educators.
I hope you find this review of the latest developments in thoracic cancers of benefit to you in
your practice. If you would like to share your thoughts with us we would welcome your
comments. Please send any correspondence to [email protected].
I would like to thank our ETOP members Solange Peters and Martin Reck for their roles as
Editors – for prioritising abstracts and reviewing slide content. The slide set you see before
you would not be possible without their commitment and hard work.
Finally, we are also very grateful to Lilly Oncology for their financial, administrative and
logistical support in the realisation of this activity.
Yours sincerely,
Rolf Stahel
President, ETOP Foundation Council
ETOP Medical Oncology Slide Deck Editors 2018
Focus: advanced NSCLC (not radically treatable stage III & stage IV)
Dr Solange Peters
Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland
Focus: other malignancies, SCLC, mesothelioma, rare tumours
Dr Martin Reck
Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany
Contents
• Screening and biomarkers
• Early stage and locally advanced NSCLC – Stages I, II and III
• Advanced NSCLC – Not radically treatable stage III and stage IV
– First line
– Later lines
• Other malignancies
– SCLC, mesothelioma and thymic epithelial tumours
Screening and biomarkers
65PD: High tumor mutational burden (TMB) and PD-L1 have similar predictive
utility in 2L+ NSCLC patients (pts) treated with anti-PD-L1 and anti-CTLA-4
– Higgs BW, et al
• Study objective
– To compare the utility of high TMB and PD-L1 to predict outcomes in patients
with non-squamous NSCLC who were treated with durvalumab and
tremelimumab
• Methods
– Immunotherapy-naïve patients (n=213) with non-squamous EGFR and ALK wild-
type NSCLC who had progressed after one prior platinum-based therapy were
enrolled to durvalumab 20 mg/kg q4w for up to 12 months with tremelimumab
1 mg/kg q4w for 4 cycles
– Tumour PD-L1 expression classified as ≥25% or <25% using the Ventana PD-L1
(SP263) assay
– DNA sequencing was performed on 106 of 200 (53%) available tumour biopsies
and TMB high defined as the top tertile of values (11 mut/Mb)
Higgs BW, et al. Ann Oncol 2018;29(suppl 5):Abstr 65PD
65PD: High tumor mutational burden (TMB) and PD-L1 have similar predictive
utility in 2L+ NSCLC patients (pts) treated with anti-PD-L1 and anti-CTLA-4
– Higgs BW, et al
• Key results
– There was no appreciable correlation between TMB and PD-L1
Higgs BW, et al. Ann Oncol 2018;29(suppl 5):Abstr 65PD
Low linear correlation
between PD-L1 levels and TMB
PD-L1 vs. TMB
status overlap
PD
-L1
TC
, %
TMB, mutations/Mb
30
40
50
60
70
80
90
100
20
10
00 5 10 20 25 30 35 5540 45 5015
rho=0.3
PD-L1
≥25%
n=16
16%
TMB
high
n=17
17%
n=18
17%
PD-L1 <25%/
TMB low
n=52
50%
65PD: High tumor mutational burden (TMB) and PD-L1 have similar predictive
utility in 2L+ NSCLC patients (pts) treated with anti-PD-L1 and anti-CTLA-4
– Higgs BW, et al
• Key results
• Conclusions
– In this study of patients with non-squamous NSCLC TMB and PD-L1 expression
were not correlated
– Patients who were TMB high (≥11 mut/Mb) had improved ORR, PFS and OS
Higgs BW, et al. Ann Oncol 2018;29(suppl 5):Abstr 65PD
TMB
≥11 mut/Mb
(n=37)
TMB
<11 mut/Mb
(n=69)
PD-L1
≥25%
(n=57)
PD-L1
<25%
(n=136)
Total*
(N=213)
PFS
Median, months (95%CI) 7.1 (1.7, 9.1) 1.7 (1.6, 3.6) 7.1 (3.5, 9.2) 3.3 (1.7, 3.6) 3.5 (1.8, 4.0)
12-month PFS, % (95%CI) 26.8 (13.8, 41.6) 12.6 (5.6, 22.6) 34.2 (21.9, 46.8) 10.0 (4.8, 17.5) 17.6 (12.4, 23.6)
OS
Median, months (95%CI) NE (7.9, NE) 8.9 (4.8, NE) 15.5 (15.4, NE) 9.5 (6.7, NE) 15.4 (10.0, NE)
12-month OS, % (95%CI) 61.2 (42.4, 75.5) 43.0 (30.4, 55.0) 71.6 (57.3, 81.9) 47.3 (38.2, 55.9) 53.8 (46.4, 60.6)
*20 patients had unknown PD-L1 expression; NE, not estimable
1136PD: Discrepancy of tumor neoantigen burden between primary lesions and
matched metastases in lung cancer – Jiang T, et al
• Study objective
– To compare neoantigen landscapes in primary tumours and metastases in patients with
lung cancer
• Key result
• Conclusion
– Neoantigen landscapes were similar in primary tumours and metastases, however, only
20% of neoantigens were shared
Jiang T, et al. Ann Oncol 2018;29(suppl 5):Abstr 1136PD
Comparison of neoantigens in primary tumours and metastases by baseline characteristics
0
400
800
1200
1600
2000
53 61 69 62 68 57 45 58 54 87 51 61 60 47
Primary
Female
Yes
SCLC
Metastasis
Male
No
LUAD
Ne
oa
ntig
en c
oun
ts
Age, years
Gender
Smoking
Histology
LM
15
LM
18
LM
21
LM
14
LM
10
LM
08
LM
13
LM
16
LM
11
LM
19
BM
12
BM
14
BM
18
BM
15
LUSC
Gender
Smoking
Histology
Early stage and locally advanced
NSCLC – Stages I, II and III
LBA48_PR: CTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-
adjuvant treatment for stage IIIA–N2 EGFR-mutation non-small-cell lung cancer
(EMERGING): a randomised study – Zhong W, et al
• Study objective
– To investigate the efficacy of erlotinib vs. gemcitabine + cisplatin as neoadjuvant/
adjuvant treatment in patients with locally advanced EGFR mutant NSCLC
Zhong W, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA48_PR
Primary endpoint
• ORR
Secondary endpoints
• Downstaging rates of pathological lymph nodes,
pCR, PFS, OS, safety
R
1:1
Stratification
• Lymph node status
• Histology
• Smoking
• Sex
Key patient inclusion criteria
• Treatment naïve IIIA-N2
NSCLC
• EGFR activating mutation
• ECOG PS 0–1
(n=72)Gemcitabine +
cisplatin* q3w
for 2 cycles
(n=35)
Erlotinib 150 mg/day
for 42 days
(n=37)
*Gemcitabine 1250 mg/m2 D1, 8; cisplatin 75 mg/m2 D1
Gemcitabine +
cisplatin* q3w
for 2 cycles
Erlotinib 150 mg/day
for 12 months
S
U
R
G
E
R
Y
Non-PD
LBA48_PR: CTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-
adjuvant treatment for stage IIIA–N2 EGFR-mutation non-small-cell lung cancer
(EMERGING): a randomised study – Zhong W, et al
• Key results
– ORR in the ITT population was 54.1% (95%CI 37.2, 70.9) with erlotinib vs.
34.3% (95%CI 17.7, 50.8) with gemcitabine + cisplatin (OR 2.26 [95%CI 0.87,
5.84], p=0.092)
Zhong W, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA48_PR
Erlotinib
(n=37)
Gemcitabine +
cisplatin
(n=35) p-value
Surgery, n (%) 31 (83.8) 24 (68.6) 0.129
Complete resection, n (%)
R0
R1
R2
27 (73.0)
27 (73.0)
1 (2.7)
3 (8.1)
22 (62.9)
22 (62.9)
1 (2.9)
1 (2.9)
0.358
Lymph node downstage, n (%)
N2pN0
N2pN1
N2pN2
4 (10.8)
3 (8.1)
1 (2.7)
27 (73.0)
1 (2.9)
1 (2.9)
0 (0)
23 (65.7)
0.185
LBA48_PR: CTONG 1103: Erlotinib versus gemcitabine plus cisplatin as neo-
adjuvant treatment for stage IIIA–N2 EGFR-mutation non-small-cell lung cancer
(EMERGING): a randomised study – Zhong W, et al
• Key results
• Conclusion
– Erlotinib in the neoadjuvant setting for EGFRm NSCLC improved ORR, MPR,
R0 resection and lymph node downstaging and the safety profile was in line with
previous reportsZhong W, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA48_PR
100
80
60
40
20
0
Pro
gre
ssio
n-f
ree s
urv
iva
l, %
0
37
35
6
28
20
12
21
13
18
16
4
24
7
3
30
2
1
36
0
0
42
Time, months
76.7%
49.0% 36.4%
14.4%
Group Events mPFS, months (95%CI)
Erlotinib (n=37) 20 21.5 (19.3, 23.6)
Gemcitabine +
cisplatin (n=35)26 11.9 (9.1, 14.7)
HR 0.42 (95%CI 0.23, 0.76), p=0.003
No.at risk
Erlotinib
Gemcitabine
+ cisplatin
PFS (ITT population)
LBA49: Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for
resectable non-small cell lung cancer (NSCLC) – Cascone T, et al
• Study objective
– To investigate the efficacy and safety of nivolumab alone or in combination with
ipilimumab in patients with untreated resectable NSCLC
Cascone T, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA49
Primary endpoint
• Major pathological response (MPR)
Secondary endpoints
• Safety, perioperative mortality and
morbidity, ORR, RFS, OS, complete
resection rate, pCR
R
1:1
Stratification
• Stage
Key patient inclusion criteria
• Stage I–IIIA NSCLC
• Eligible for surgery
(n=44) Ipilimumab 1 mg/kg D1
+ nivolumab 3 mg/kg
D1, 15, 29
(n=18)
Nivolumab 3 mg/kg
D 1, 15, 29
(n=18)
SurgeryAdjuvant
therapy
SurgeryAdjuvant
therapy
LBA49: Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for
resectable non-small cell lung cancer (NSCLC) – Cascone T, et al
• Key results
Cascone T, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA49
Total NivolumabNivolumab +
ipilimumab
Evaluable (resected) n=26 n=14 n=12
MPR + pCR, n (%) 8 (31) 4 (28) 4 (33)
0% viable tumour cells (pCR), n (%) 5 (19) 2 (14) 3 (25)
1–10% viable tumour cells, n (%) 3 (11) 2 (14) 1 (8)
Overall (resected + unresectable) n=31 n=16 n=15
MPR + pCR, n (%) 8 (26) 4 (25) 4 (27)
0% viable tumour cells (pCR), n (%) 5 (16) 2 (13) 3 (20)
1–10% viable tumour cells, n (%) 3 (10) 2 (13) 1 (7)
–21
LBA49: Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for
resectable non-small cell lung cancer (NSCLC) – Cascone T, et al
• Key results (cont.)
• Conclusions
– In resected patients with NSCLC, neoadjuvant nivolumab or nivolumab +
ipilimumab induced an MPR rate of 31%
– Greater TIL proliferation and activation was demonstrated with neoadjuvant
nivolumab and nivolumab + ipilimumab compared with untreated tumours
Cascone T, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA49
Evaluable
Total
(n=32)
Nivolumab
(n=16)
Nivolumab +
ipilimumab
(n=16)
Response,
n (%)
CR
PR
SD
PD
1 (3)
6 (19)
19 (59)
6 (19)
0 (0)
5 (31)
8 (50)
3 (19)
1 (6)
1 (6)
11 (69)
3 (19)
ORR, n/N
(%)
7/32
(22)
5/16
(31)
2/16
(12)
-100
-80
-60
-40
-20
0
20
40
*
*
Overa
ll %
change in t
um
our
siz
e f
rom
baselin
e
Nivolumab (evaluable)
(n=16)
-100
-80
-60
-40
-20
0
20
40
Nivolumab + ipilimumab
(evaluable) (n=16)
*
*
21 1413
7 4 3 2 0 0
–2–12
–30–34
–39 –39–45
2214 12 10
40
–6
–16–17–18–19
–31
–100
–20
35
*Considered SD in target lesion but overall PD due to new
radiographic lesions
Radiographic responses
1363O: Efficacy and safety evaluation based on time from completion of
radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC
– Faivre-Finn C, et al
• Study objective
– To investigate the efficacy and safety outcomes of durvalumab in the PACIFIC
trial based on PD-L1 expression and the components of chemoradiation
received prior to durvalumab or placebo
Faivre-Finn C, et al. Ann Oncol 2018;29(suppl 5):Abstr 1363O
Primary endpoints
• PFS by BICR, OS
Secondary endpoints
• ORR, DoR and TTDM by BICR, PFS2
by investigator, safety, PROs
Stratification
• Age
• Sex
• Smoking history
Key patient inclusion criteria
• Stage III NSCLC
• No progression after ≥2 cycles of
platinum-CRT
• Pre-cCRT tumour tissue for PD-L1
testing if available
• WHO PS 0–1
(n=713)
Placebo q2w
(n=237)
Durvalumab 10 mg/kg q2w
(n=476)
R
1:1
1363O: Efficacy and safety evaluation based on time from completion of
radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC
– Faivre-Finn C, et al
• Key results
– Median OS in the PD-L1 TC ≥1% was NR (95%CI NR, NR) with durvalumab
and 29.1 months (95%CI 17.7, NR) for placebo; HR 0.53 (95%CI 0.36, 0.77)
– Median OS in the PD-L1 TC <1% was NR (95%CI 20.8, NR) with durvalumab
and NR (95%CI 27.3, NR) for placebo; HR 1.36 (95%CI 0.79, 2.34)
Events/
patients (%)
Median PFS,
months
(95%CI)
Durvalumab 84/212 (39.6) 17.8 (16.9, NR)
Placebo 59/91 (64.8) 5.6 (3.6, 11.0)
HR 0.46 (95%CI 0.33, 0.64)
PFS (BICR) by PD-L1 TC ≥1% PFS (BICR) by PD-L1 TC <1%
Events/
patients (%)
Median PFS,
months
(95%CI)
Durvalumab 49/90 (54.4) 10.7 (7.3, NR)
Placebo 40/58 (69.0) 5.6 (3.7, 10.6)
HR 0.73 (95%CI 0.48, 1.11)
Pro
ba
bili
ty o
f P
FS
1.0
0.8
0.6
0.4
0.2
0.0
0 3 6 9 12 15 21 24 2718Time from randomisation, months
212
91
174
59
143
39
127
34
82
20
52
13
14
4
1
3
0
0
30
8
No. at risk
Durvalumab
PlaceboP
rob
ab
ility
of P
FS
1.0
0.8
0.6
0.4
0.2
0.0
0 3 6 9 12 15 21 24 2718Time from randomisation, months
90
58
70
45
51
25
42
21
23
14
9
8
1
0
0
0
0
0
4
5
No. at risk
Durvalumab
Placebo
Faivre-Finn C, et al. Ann Oncol 2018;29(suppl 5):Abstr 1363O
1363O: Efficacy and safety evaluation based on time from completion of
radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC
– Faivre-Finn C, et al
• Key results (cont.)
• Conclusions
– Durvalumab led to improvement in PFS and OS in the PD-L1 ≥1% subgroup
and PFS in the <1% PD-L1 subgroup
– Durvalumab improved PFS and OS regardless of chemoradiation received prior
to therapyFaivre-Finn C, et al. Ann Oncol 2018;29(suppl 5):Abstr 1363O
Events / patients (%)
HR (95%CI) Durvalumab Placebo
Induction
chemotherapy
Yes
No
59/123 (48.0)
155/353 (43.9)
49/68 (72.1)
108/169 (63.9)
Platinum Cisplatin
Carboplatin
115/266 (43.2)
91/199 (45.7)
87/129 (67.4)
65/102 (63.7)
Taxane Yes
No
97/207 (46.9)
117/269 (43.5)
72/112 (64.3)
85/125 (68.0)
Etoposide Yes
No
49/117 (41.9)
165/359 (46.0)
34/52 (65.4)
123/185 (66.5)
Vinorelbine Yes
No
58/124 (46.8)
156/352 (44.3)
42/59 (71.2)
115/178 (64.6)
Dose of
radiotherapy
<60 Gy
60–66 Gy
>66 Gy
16/38 (42.1)
187/407 (45.9)
10/30 (33.3)
11/15 (73.3)
130/202 (64.4)
15/19 (78.9)
Placebo betterDurvalumab better
0.25 0.5 1 2
PFS (BICR)
Advanced NSCLCNot radically treatable stage III and stage IV
First line
LBA10: Primary results of ALESIA: A randomised, phase III, open-label study of
alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced
NSCLC – Zhou C, et al
• Study objective
– To investigate safety and efficacy of 1L alectinib vs. crizotinib in Asian patients
with ALK+ NSCLC in the ALESIA study
Zhou C, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA10
Primary endpoint
• PFS (investigator-assessed)
Secondary endpoints
• PFS by IRC, time to CNS progression,
ORR and DoR (investigator-assessed),
OS, CNS ORR, safety, QoL, PK
Stratification
• ECOG PS (0/1 vs. 2)
• Baseline brain metastases
Key patient inclusion criteria
• Asian patients with stage IIIB/IV
ALK+ NSCLC
• Treatment naïve
• ECOG PS 0–2
(n=187)Crizotinib 250 mg bid
(n=62)
Alectinib 600 mg bid
(n=125)
R
2:1
LBA10: Primary results of ALESIA: A randomised, phase III, open-label study of
alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced
NSCLC – Zhou C, et al
• Key result
Zhou C, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA10
Alectinib
(n=125)
Crizotinib
(n=62)
Patients with event, n (%) 26 (20.8) 37 (59.7)
Median PFS, months (95%CI) NE (20.3, NE) 11.1 (9.1, 13.0)
HR (95%CI); p-value (log-rank test) 0.22 (0.13, 0.38); <0.0001
Pro
gre
ssio
n-f
ree s
urv
iva
l, %
Time, months
100
80
60
40
20
00 3 6 9 12 15 18 21
Alectinib
Crizotinib
NE
11.1 months
Cause-specific HR
p-value (log-rank test)
0.14 (95%CI 0.06, 0.30)
<0.0001C
um
ula
tive
incid
en
ce*,
%
Time, months
60
40
20
0
0 3 6 9 12 15 18 21
Alectinib
Crizotinib
7.3%
35.5% (95%CI 23.5, 47.8)
(95%CI 3.6, 12.8)
PFS (investigator-assessed) Time to CNS progression (IRC-assessed)
*Cumulative incidence of CNS progression without prior
non-CNS progression or death
LBA10: Primary results of ALESIA: A randomised, phase III, open-label study of
alectinib vs crizotinib in Asian patients with treatment-naïve ALK+ advanced
NSCLC – Zhou C, et al
• Key result (cont.)
• Conclusions
– Alectinib led to a significant improvement in PFS and showed benefits in
regards to ORR, DoR and time to CNS progression compared with crizotinib
– The safety profile of alectinib in Asian patients was consistent with the previous
findingsZhou C, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA10
DoR
(un
co
nfirm
ed)
,%
Time, months
100
80
60
40
20
00 3 6 9 12 15 18 21
Alectinib
Crizotinib
NE
9.3 months
Response, n (%)
Alectinib
(n=125)
Crizotinib
(n=62)
ORR 114 (91.2) 48 (77.4)
CR 5 (4.0) 3 (4.8)
PR 109 (87.2) 45 (72.6)
SD 7 (5.6) 8 (12.9)
PD 2 (1.6) 4 (6.5)
Missing or
unevaluable2 (1.6) 2 (3.2)
Alectinib
(n=114)
Crizotinib
(n=48)
Median DoR, months (95%CI) NE (18.4, NE) 9.3 (7.4, NE)
HR (95%CI), p-value (log-rank test) 0.22 (0.12, 0.40); p<0.0001
DoR (investigator-assessed)
LBA50: Mechanisms of acquired resistance to first-line osimertinib: preliminary
data from the phase III FLAURA study – Ramalingam SS, et al
• Study objective
– To investigate the mechanisms of acquired resistance to osimertinib and
standard of care (gefitinib + erlotinib) in patients who progressed or discontinued
treatment in the FLAURA study
• Methods
– Patients in the FLAURA study had EGFR+ (ex19del or L858R) locally advanced
or metastatic NSCLC and were treated with osimertinib or gefitinib + erlotinib
until progression
– Paired plasma samples were taken from patients at baseline and at
progression/discontinuation for ctDNA genomic profiling
– NGS was conducted using the Guardant360 assay or GuardantOMNI assay
– Analysis set of valid paired NGS data were available for 272 patients
• Osimertinib: 113/279 (41%)
• Gefitinib + erlotinib: 159/277 (57%)
Ramalingam SS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA50
LBA50: Mechanisms of acquired resistance to first-line osimertinib: preliminary
data from the phase III FLAURA study – Ramalingam SS, et al
• Key results
– The most common acquired resistance mechanisms in the osimertinib arm
(n=91) were:
• MET amplification (15%) and EGFR C797S mutation (7%)
• There was no evidence of acquired T790M
– The most common acquired resistance mechanisms in the gefitinib + erlotinib
arm (n=129) were:
• T790M (47%), MET amplification (4%) and HER2 amplification (2%)
• Conclusions
– There was no evidence of acquired resistance through T790M in the
osimertinib-treated patients, while MET amplification and EGFR C797S
mutations were the most common
– New mechanisms that may lead to aggressive disease biology were not
identified
Ramalingam SS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA50
LBA51: Analysis of resistance mechanisms to osimertinib in patients with EGFR
T790M advanced NSCLC from the AURA3 study – Papadimitrakopoulou VA, et al
• Study objective
– To investigate the mechanisms of acquired resistance to osimertinib in patients
who progressed or discontinued treatment in the AURA3 study
• Methods
– Patients in the AURA3 study had T790M+ locally advanced or metastatic
NSCLC and were treated with osimertinib or platinum-pemetrexed until
progression
– Paired plasma samples were taken from patients at baseline and at
progression/discontinuation for ctDNA genomic profiling
– NGS was undertaken using the Guardant360 assay
– Analysis set of valid paired NGS data were available for 113 patients
• Osimertinib: 83/279 (30%)
• Platinum-pemetrexed: 30/140 (21%)
Papadimitrakopoulou VA, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA51
LBA51: Analysis of resistance mechanisms to osimertinib in patients with EGFR
T790M advanced NSCLC from the AURA3 study – Papadimitrakopoulou VA, et al
• Key results
– Loss of T790M was seen in 49%
of patients
– Acquired EGFR mutations were
observed in 21% of patients; the
most common was C797S (14%)
– Other mutations included:
MET amplification (19%);
cell cycle gene alterations (12%);
HER2 amplification (5%);
PIK3CA amplification/mutation (5%);
oncogenic fusion (4%),
BRAF V600E (3%)
– All cases of C797X mutations were in
the cis position when co-occurring with T790M
• Conclusion
– EGFR mutations and MET amplifications were the most common acquired
resistance mechanisms to osimertinib among a diverse mixture, consistent with
previous reports Papadimitrakopoulou VA, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA51
Acquired EGFR mutations with osimertinib
(represents 21% of total patients)
C797X: 15%
(10 C797S, 1 C797G)
L792H/F
+ C797S: 1%
L792H: 1%
G796S: 1%
L718Q: 1%
Ex20ins: 1%
LBA52: Results of the GEOMETRY mono-1 phase II study for evaluation of the
MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated
advanced non-small cell lung cancer (NSCLC) – Wolf J, et al
• Study objective
– To investigate the efficacy and safety of capmatinib, a selective MET inhibitor, in
patients with METΔex14 mutated advanced NSCLC
Wolf J, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA52
Primary endpoint
• ORR by BIRC
Secondary endpoints
• DoR by BIRC
Cohort 4:
Previously treated (1–2 prior lines) for
advanced stage
Capmatinib 400 mg bid
(n=69)
Key patient inclusion criteria
• Stage IIIB/IV NSCLC
• METΔex14 determined
centrally
• EGFR wt and ALK negative
• ≥1 measureable lesion
• ECOG PS 0–1
Cohort 5b:
Treatment-naïve for advanced stage
Capmatinib 400 mg bid
(n=28)
LBA52: Results of the GEOMETRY mono-1 phase II study for evaluation of the
MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated
advanced non-small cell lung cancer (NSCLC) – Wolf J, et al
• Key results
– ORR (BIRC) in Cohort 4 (pre-treated) was 39.1% (95%CI 27.6, 51.6)
– ORR (BIRC) in Cohort 5b (treatment naïve) was 72.0% (95%CI 50.6, 87.9)
Wolf J, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA52
Be
st %
ch
an
ge
fro
m b
ase
line *
* * * * **
* * **
0
–25
–50
–75
–100
n=24†/25 PR SD PD NE
-100
-75
-50
-25
0
25
n=60†/69
*
** *
* * * * ** *
*
*Cohort 5b (treatment naïve)
Cohort 4 (pre-treated)
Be
st %
ch
an
ge
fro
m b
ase
line
*Patients still on treatment; †number of patients with measurable
disease at baseline and ≥1 post-baseline assessment
LBA52: Results of the GEOMETRY mono-1 phase II study for evaluation of the
MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated
advanced non-small cell lung cancer (NSCLC) – Wolf J, et al
• Key results
• Conclusions
– In patients with METΔex14 advanced NSCLC, capmatinib shows promising
results
– The differential benefit of 1L over later-line treatment highlights the need for
prompt targeted treatment in this patient group
Wolf J, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA52
AE, n (%)
Cohort 4 (pre-treated)
(n=69)
Cohort 5b (treatment naive)
(n=28)
All patients
(N=302)
All grades Grade 3/4 All grades Grade 3/4 All grades Grade 3/4
Any 60 (87.0) 33 (47.8) 27 (96.4) 14 (50.0) 253 (83.8) 100 (33.1)
Peripheral oedema 31 (44.9) 10 (14.5) 18 (64.3) 1 (3.6) 122 (40.4) 19 (6.3)
Nausea 24 (34.8) 0 11 (39.3) 0 99 (32.8) 5 (1.7)
Vomiting 13 (18.8) 0 4 (14.3) 0 58 (19.2) 6 (2.0)
Blood creatinine increased 15 (21.7) 0 7 (25.0) 0 58 (19.2) 0
Fatigue 9 (13.0) 4 (5.8) 2 (7.1) 1 (3.6) 40 (13.2) 10 (3.3)
Decreased appetite 10 (14.5) 1 (1.4) 5 (17.9) 0 40 (13.2) 3 (1.0)
Diarrhoea 8 (11.6) 0 3 (10.7) 0 35 (11.6) 0
LBA53: IMpower130: Progression-free survival (PFS) and safety analysis from a
randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without
atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous
NSCLC – Cappuzzo F, et al
• Study objective
– To investigate the efficacy and safety of atezolizumab combined with carboplatin
+ nab-paclitaxel vs. carboplatin + nab-paclitaxel in chemotherapy-naïve patients
with stage IV non-squamous NSCLC
Cappuzzo F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA53
Co-primary endpoints
• Investigator-assessed PFS and OS
(ITT-WT* population)
Secondary endpoints
• OS and PFS (ITT population and by
PD-L1 expression), ORR, safety
R
2:1
PD/
toxicity
Loss of
clinical
benefit/
toxicity
Stratification
• Sex
• Baseline liver metastases
• PD-L1 tumour expression
Key patient inclusion
criteria
• Stage IV non-
squamous NSCLC
• Chemotherapy-naïve
• Pre-treated EGFR
mutated or ALK
translocation (TKI)
(n=723; ITT-WT* n=679)
Carboplatin AUC 6 q3w +
nab-paclitaxel 100 mg/m2 q3w
Atezolizumab 1200 mg q3w +
carboplatin AUC 6 q3w +
nab-paclitaxel 100 mg/m2 q3w
*ITT-WT population, randomised patients excluding
those with EGFR or ALK mutations
Best supportive care
or pemetrexed q3w
Atezolizumab
Induction treatment (4 or 6 cycles) Maintenance treatment
OS rate, % 1-year 2-year
Atezolizumab
+ CnP63.1 39.6
CnP 55.5 30.0
LBA53: IMpower130: Progression-free survival (PFS) and safety analysis from a
randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without
atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous
NSCLC – Cappuzzo F, et al
• Key results
Cappuzzo F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA53
PFS rate, % 6-month 12-month
Atezolizumab
+ CnP56.1 29.1
CnP 42.5 14.1
Investigator-assessed PFS (ITT-WT)
PF
S, %
Months after randomisation
1.0
0.8
0.6
0.4
0.2
0.0
0
451
228
1
432
214
2
383
174
3
351
150
4
329
136
5
281
110
30
No. at risk
Atezo + CnP
Chemo
6
242
90
7
213
75
8
183
61
9
157
48
10
138
40
11
132
35
12
119
29
13
108
23
14
83
18
15
78
15
16
62
7
17
60
6
18
41
5
19
36
5
20
29
3
21
23
3
22
13
2
23
12
2
24
7
1
25
4
1
26
1
27 28 29
Median follow-up: ~19 months
HR 0.64
(95%CI 0.54, 0.77)
p<0.0001
OS (ITT-WT)
OS
, %
Months after randomisation
1.0
0.8
0.6
0.4
0.2
0.0
0
451
228
1
435
218
2
422
206
3
400
190
4
384
176
5
365
167
30
4
No. at risk
Atezo + CnP
Chemo
6
351
161
7
333
154
8
315
147
9
305
136
10
294
132
11
284
124
12
268
119
13
253
109
14
217
96
15
194
90
16
167
75
17
147
65
18
129
58
19
103
49
20
88
39
21
75
31
31
2
22
59
24
32
1
23
49
17
3324
40
13
3425
29
9
26
19
8
27
12
3
28
10
1
29
6
HR 0.79
(95%CI 0.64, 0.98)
p=0.033
Median: 5.5 mo
(95%CI 4.4, 5.9)
Median: 7.0 mo
(95%CI 6.2, 7.3)
Median: 13.9 mo
(95%CI 12.0, 18.7)
Median: 18.6 mo
(95%CI 16.0, 21.2)
LBA53: IMpower130: Progression-free survival (PFS) and safety analysis from a
randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without
atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous
NSCLC – Cappuzzo F, et al
• Key results (cont.)
• Conclusions
– In the ITT-WT population atezolizumab + chemotherapy showed benefit in PFS
and OS, which was maintained across all PD-L1 subgroups
– No new safety signals were observed with the combination of atezolizumab +
chemotherapyCappuzzo F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA53
PFS by baseline PD-L1 status (ITT-WT)
Atezo + CnP
(n=88)
CnP
(n=42)
Median PFS,
mo (95%CI)
6.4
(5.49, 9.76)
4.6
(3.22, 7)
HR (95%CI) 0.51 (0.34, 0.77)
Atezo + CnP
(n=128)
CnP
(n=65)
Median PFS,
mo (95%CI)
8.3
(7.16, 10.35)
6.0
(5.29, 6.93)
HR (95%CI) 0.61 (0.43, 0.85)
Atezo + CnP
(n=235)
CnP
(n=121)
Median PFS,
mo (95%CI)
6.2
(5.52, 7.16)
4.7
(4.11, 5.72)
HR (95%CI) 0.72 (0.56, 0.91)
PF
S, %
100
80
60
40
20
0
0
88
42
2
76
32
4
64
23
No. at risk
Atezo+CnP
Chemo
6
43
18
8
34
11
10
28
9
12
22
4
14
17
1
16
12
18
8
20
6
22
4
24
3
26 28
PD-L1-high
TC3 or IC3
Time, months
30
PD-L1-low
TC1/2 or IC1/2
PF
S, %
100
80
60
40
20
0
0
128
65
2
113
49
4
103
42
6
83
30
8
64
20
10
51
12
12
42
9
14
28
5
16
16
3
18
9
1
20
6
22
4
24
2
26 28
Time, months
30
PD-L1-negative
TC0 and IC0
PF
S, %
100
80
60
40
20
0
0
235
121
2
194
93
4
162
71
306
116
42
8
85
30
10
59
19
12
55
16
14
38
9
16
34
4
18
24
4
20
17
3
22
5
2
24
2
1
26
1
28
Time, months
LBA54: IMpower132: efficacy of atezolizumab (atezo) + carboplatin
(carbo)/cisplatin (cis) + pemetrexed (pem) as 1L treatment in key subgroups with
stage IV non-squamous non-small cell lung cancer (NSCLC) – Barlesi F, et al
• Study objective
– To investigate the PFS benefit of atezolizumab combined with carboplatin or
cisplatin + pemetrexed in patients from IMpower132 in an exploratory analysis
stratified by race, age, smoking history or liver metastasis at baseline
Barlesi F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA54
Exploratory endpoints
• Clinical and biomarker subgroup analysis
R
1:1
PD/
loss of
clinical
benefit
Stratification
• Sex
• Smoking status
• ECOG PS
• Chemotherapy regimen
Key patient inclusion
criteria
• Stage IV non-
squamous NSCLC
• Chemotherapy-naïve
• Without EGFR or ALK
genetic alteration
(n=578) Carboplatin or cisplatin +
pemetrexed*
Atezolizumab +
carboplatin or cisplatin +
pemetrexed*
Pemetrexed*
Atezolizumab +
pemetrexed*
Induction therapy (4 or 6 cycles) Maintenance therapy
*Atezolizumab 1200 mg IV q3w; carboplatin AUC 6 mg/mL/min IV q3w;
cisplatin 75 mg/m2 IV q3w; pemetrexed 500 mg/m2 IV q3w
PD/
loss of
clinical
benefit
LBA54: IMpower132: efficacy of atezolizumab (atezo) + carboplatin
(carbo)/cisplatin (cis) + pemetrexed (pem) as 1L treatment in key subgroups with
stage IV non-squamous non-small cell lung cancer (NSCLC) – Barlesi F, et al
• Key results
• Conclusion– Atezolizumab added to carboplatin/cisplatin + pemetrexed improved PFS across several
subgroups including patients from Asia, never smokers, those who were older and those
without liver metastases at baseline, but currently has not shown improvement in OSBarlesi F, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA54
PF
S, %
Time, months
1.0
0.8
0.6
0.4
0.2
0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 2019 21 22
Median PFS (95%CI), mos
HR (95%CI)
Non-Asian patients
Atezolizumab + PP
6.9 (5.9, 8.1)
PP
5.0 (4.2, 5.7)0.65 (0.53, 0.81)
Atezolizumab + PP (n=221)
PP (n=221)
PF
S, %
Time, months
1.0
0.8
0.6
0.4
0.2
0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 2019 21 22
Median PFS (95%CI), mos
HR (95%CI)
Asian patients
Atezolizumab + PP
10.2 (8.3, 15.3)
PP
5.3 (4.3, 6.7)
0.42 (0.28, 0.63)
Atezolizumab + PP (n=71)
PP (n=65)
PF
S, %
Time, months
1.0
0.8
0.6
0.4
0.2
0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 2019 21 22
Median PFS (95%CI), mos
HR (95%CI)
Former/current smokersAtezolizumab + PP
7.5 (6.3, 8.4)
PP
5.1 (4.3, 5.6)
0.61 (0.50, 0.74)
Atezolizumab + PP (n=225)
PP (n=226)
PF
S, %
Time, months
1.0
0.8
0.6
0.4
0.2
0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 2019 21 22
Median PFS (95%CI), mos
HR (95%CI)
Never smokersAtezolizumab + PP
8.6 (6.5, 15.4)
PP
5.5 (4.0, 8.3)
0.49 (0.28, 0.87)
Atezolizumab + PP (n=37)
PP (n=30)
LBA55: Primary efficacy results from B-F1RST, a prospective phase II trial
evaluating blood-based tumour mutational burden (bTMB) as a predictive
biomarker for atezolizumab (atezo) in 1L nonsmall cell lung cancer (NSCLC)
– Kim ES, et al
• Study objective
– To investigate the use of bTMB as a predictive biomarker for atezolizumab
monotherapy in 1L NSCLC
Kim ES, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA55
Co-primary endpoints
• Investigator-assessed ORR and PFS
(using pre-specified bTMB cut-off of 16)
Secondary endpoints
• Safety, investigator-assessed DoR and OS
Atezolizumab 1200 mg q3w
(biomarker evaluable
population n=119)
PD/toxicity/
loss of
benefit
Key patient inclusion criteria
• Stage IIIB/IVA locally advanced
or metastatic NSCLC
• Immunotherapy naïve
• PD-L1 unselected
• ECOG PS 0–1
(n=152)
LBA55: Primary efficacy results from B-F1RST, a prospective phase II trial
evaluating blood-based tumour mutational burden (bTMB) as a predictive
biomarker for atezolizumab (atezo) in 1L nonsmall cell lung cancer (NSCLC)
– Kim ES, et al
• Key results
Kim ES, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA55
ORR per RECIST v1.1
bTMB subgroups
14.5%16.3%
28.6%
36.8%
10.1%
5.7% 4.4% 5%
0
5
10
15
20
25
30
35
40
Ove
rall
resp
on
se r
ate
, %
ITT
(N=152)
BEP
(n=119)
High
(n=49)
Low
(n=70)
High
(n=28)
Low
(n=91)
High
(n=19)
Low
(n=100)
PR CR
≥10 cut-off ≥16 cut-off ≥20 cut-off
p<0.0001
p=0.0002
p=0.0595
LBA55: Primary efficacy results from B-F1RST, a prospective phase II trial
evaluating blood-based tumour mutational burden (bTMB) as a predictive
biomarker for atezolizumab (atezo) in 1L nonsmall cell lung cancer (NSCLC)
– Kim ES, et al
• Key results (cont.)
• Conclusion
– In patients with NSCLC treated with atezolizumab monotherapy a numerical
improvement in outcomes was seen in those with a bTMB cut-off of ≥16 Kim ES, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA55
bTMB high
(n=28)
bTMB low
(n=91)
Median PFS,
months (90%CI)4.6 (1.6, 11.0) 3.7 (2.6, 4.3)
HR (90%CI) 0.66 (0.42, 1.02)
p-value 0.12
PFS in bTMB high (≥16) vs. low (<16) subgroups
Pro
gre
ssio
n-f
ree s
urv
iva
l, %
Time, months
100
80
60
40
20
0
0
28
91
1
27
86
2
17
56
3
14
43
No. at risk
High (≥16)
Low (<16)
High, ≥16 (n=28)
Low, <16 (n=91)
6-month PFS
41.6% vs. 32.8%
9-month PFS
37.4% vs. 9.7%
4
14
39
5
13
28
6
11
21
7
8
11
8
8
5
9
8
4
10
5
3
11
4
3
12
3
1
13
2
14
1
LBA58: Intracranial efficacy of brigatinib (BRG) vs crizotinib (CRZ) in the
phase 3 ALTA-1L trial – Popat S, et al
• Study objective
– To investigate the intracranial efficacy of brigatinib vs. crizotinib in ALK inhibitor-
naïve patients with advanced ALK+ NSCLC in the ATLA-1L study
Popat S, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA58
PD/toxicity/
discontinuation
Stratification
• Brain metastases at baseline
• Prior chemotherapy
Key patient inclusion criteria
• Stage IIIb/IV NSCLC
• ALK+ (based on local ALK
testing)
• No prior ALK inhibitor
• ≤1 prior systemic therapy
• Brain metastases were
allowed
(n=275)
Crizotinib 250 mg bid
(n=138)
Brigatinib 180 mg/day
(90 mg/day for 7 day lead-in)
(n=137)
Primary endpoint
• PFS (BIRC-assessed)
Secondary endpoints
• ORR, intracranial ORR, intracranial PFS,
OS, safety
PD*/toxicity/
discontinuation
*Crossover to brigatinib permitted at PD
R
1:1
LBA58: Intracranial efficacy of brigatinib (BRG) vs crizotinib (CRZ) in the
phase 3 ALTA-1L trial – Popat S, et al
• Key results
• Conclusion
– In patients with advanced ALK+ NSCLC, brigatinib demonstrated superior intracranial
efficacy vs. crizotinib, with significantly higher intracranial response and improved
intracranial PFS in those with brain metastasesPopat S, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA58
Whole body BIRC-assessed PFS by brain metastases at baseline
Treatment
Pts with
events, n (%)
Median PFS,
months
(95%CI)
1-year PFS rate,
% (95%CI)
Brigatinib (n=40) 8 (20) NR 75 (56, 87)
Crizotinib (n=41) 24 (59) 5.6 (3.8, 11.1) 25 (8, 46)
With brain metastases
PF
S,
% o
f p
atie
nts
Time, months
100
80
60
40
20
00 3 6 9 12 15 18
HR 0.20 (95%CI 0.09, 0.46)
p<0.0001 by log-rank test
Brigatinib (n=40)
Crizotinib (n=41)
Treatment
Pts with
events, n (%)
Median PFS,
months
(95%CI)
1-year PFS rate,
% (95%CI)
Brigatinib (n=97) 28 (29) NR 63 (50, 74)
Crizotinib (n=41) 39 (40) 11.1 (9.2, NR) 49 (36, 61)
PF
S,
% o
f p
atie
nts
Time, months
100
80
60
40
20
00 3 6 9 12 15 18
HR 0.72 (95%CI 0.44, 1.18)
p=0.20 by log-rank test
Brigatinib (n=97)
Crizotinib (n=97)
Without brain metastases
1377O: Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive
(MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small lung
cancer (NSCLC) – Wu Y, et al
• Study objective
– To investigate the efficacy and safety of tepotinib + gefitinib vs. chemotherapy in
Asian patients with advanced MET+/EGFR+T790M- NSCLC
Wu Y, et al. Ann Oncol 2018;29(suppl 5):Abstr 1377O
Primary endpoint
• PFS (investigator-assessed)
Secondary endpoints
• ORR, safety
R*
PD/
toxicity
PD/
toxicity
Stratification
• MET+ type (IHC2+, IHC3+ or MET amplification)
• Prior EGFR-TKI therapy
Key patient inclusion criteria
• Locally-advanced/metastatic IV
NSCLC
• EGFR+, T790M–, MET+
• Asian
• Resistance to prior EGFR TKI
• No prior HGF/MET pathway-
directed therapy
(n=55)
Chemotherapy:
Pemetrexed 500 mg/m2 q3w+
cisplatin 75 mg/m2 or
carboplatin AUC 5 or 6 q3w
(n=24)
Tepotinib 500 mg/day
+ gefitinib 250 mg/day
(n=31)
*Initially 1:1 and changed to 2:1 at protocol amendment (30 Sept 2016)
1377O: Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive
(MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small lung
cancer (NSCLC) – Wu Y, et al
• Key results
– In the MET IHC3+ subgroup (n=34) median PFS was 8.3 months with tepotinib + gefitinib
and 4.4 months with chemotherapy (HR 0.35 [95%CI 0.17, 0.74])
– In the MET amplification subgroup (n=19) median PFS was 21.2 months with tepotinib +
gefitinib and 4.2 months with chemotherapy (HR 0.17 [95%CI 0.05, 0.57])
Wu Y, et al. Ann Oncol 2018;29(suppl 5):Abstr 1377O
Tepotinib + gefitinib
(n=31)
Chemotherapy
(n=24)
Events 23 19
Median PFS, months (90%CI) 4.9 (3.9, 6.9 4.4 (4.2, 6.8)
Stratified HR (90%CI) 0.71 (0.36, 1.39)
KM
estim
ate
fo
r P
FS
Time, months
1.0
0.8
0.6
0.4
0.2
0.0
0
31
24
3
20
16
6
11
7
12
1
0
18
1
0
24
0
0
30
0
0
No. at risk
Tep + gef
Chemo
Investigator-assessed PFS (ITT population)
Tepotinib + gefitinib
Chemotherapy
1377O: Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive
(MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small lung
cancer (NSCLC) – Wu Y, et al
• Key results
– Tepotinib + gefitinib was generally well tolerated, with TEAEs leading to discontinuation in
9.7% of patients compared with 4.3% in the chemotherapy group
• Conclusion
– In patients with advanced NSCLC and MET amplifications, improvements in PFS were
observed with tepotinib + gefitinib, indicating that MET may be considered as a biomarker
for treatment with tepotinib
Wu Y, et al. Ann Oncol 2018;29(suppl 5):Abstr 1377O
Tepotinib + gefitinib Chemotherapy
Odds ratio
(90%CI)
Responders*
n/N
ORR, %
(90%CI)
Responders*
n/N
ORR, %
(90%CI)
Overall (n=55) 14/3145.2
(29.7, 61.3) 8/24
33.3
(17.8, 52.1)
1.99
(0.56, 6.87)
MET IHC3+ (n=34) 13/1968.4
(47.0, 85.3)5/15
33.3
(14.2, 57.7)
4.33
(1.03, 18.33)
MET amplification (n=19) 8/1266.7
(39.1, 87.7)3/7
42.9
(12.9, 77.5)
2.67
(0.37, 19.56)
*No confirmation required
1379PD: Impact of the EML4-ALK variant on the efficacy of alectinib (ALC) in
untreated ALK+ advanced NSCLC (aNSCLC) in the global phase III ALEX study
– Dziadziuszko R, et al
• Study objective
– To assess efficacy of alectinib vs. crizotinib in the ALEX trial in patients with
ALK+ advanced NSCLC stratified by EML4-ALK fusion variants
• Methods
– FOUNDATIONACT and FOUNDATIONONE NGS platforms were used to
determine the ALK fusion variants in plasma and tissue BEP subgroups
Dziadziuszko R, et al. Ann Oncol 2018;29(suppl 5):Abstr 1379PD
Key patient inclusion criteria
• ALK+ NSCLC
• No prior treatment for
NSCLC
• ECOG PS 0–2
(n=303)
Crizotinib 250 mg
bid
Alectinib 600 mg
bid
PD/death/
withdrawal
PD/death/
withdrawal
R
1:1
1379PD: Impact of the EML4-ALK variant on the efficacy of alectinib (ALC) in
untreated ALK+ advanced NSCLC (aNSCLC) in the global phase III ALEX study
– Dziadziuszko R, et al
• Key results
• Conclusion
– In patients with ALK+ NSCLC alectinib demonstrated greater efficacy than
crizotinib, regardless of EML4-ALK variant
Dziadziuszko R, et al. Ann Oncol 2018;29(suppl 5):Abstr 1379PD
PFS (investigator-assessed)
Plasma BEP subgroup Tissue BEP subgroup
ALK V1 ALK V2 ALK V3a/b
Su
rviv
al p
rob
ab
ility
1.0
0.8
0.6
0.4
0.2
3 6 12 15 18 21 2490
0.0
Time, months
EML4-ALK V1: 7.4
EML4-ALK V2: 8.8
EML4-ALK V3a/b: 9.1
Median PFS, months
Crizotinib
1.0
0.8
0.6
0.4
0.2
0.0
Time, months
EML4-ALK V1: NE
EML4-ALK V2: 14.9
EML4-ALK V3a/b: NE
Median PFS, months
Alectinib
3 6 1215 18212490 2730
1.0
0.8
0.6
0.4
0.2
3 6 12 15 18 21 2490
0.0
Time, months
EML4-ALK V1: 12.9
EML4-ALK V2: 8.8
EML4-ALK V3a/b: 14.6
Median PFS, months
Crizotinib
1.0
0.8
0.6
0.4
0.2
0.0
EML4-ALK V1: NE
EML4-ALK V2: 11.5
EML4-ALK V3a/b: NE
Median PFS, months
Alectinib
Time, months
3 6 1215 18212490 2730
1380PD: Efficacy of lorlatinib in patients (pts) with ROS1-positive advanced
non-small cell lung cancer (NSCLC) and ROS1 kinase domain mutations
– Solomon BJ, et al
• Study objective
– To investigate molecular profiling of patients with ROS1+ advanced NSCLC in
the B7461001 study of lorlatinib
• Methods
– Patients with locally advanced or metastatic NSCLC with ROS1 rearrangements
were enrolled in the phase 1/2 study
• Patients were treatment-naïve in the advanced setting of PD after ≥1 prior ROS1
inhibitor (phase 1) or any number of prior therapies (phase 2)
– Lorlatinib was orally administered in continuous 21-day cycles with escalating
doses (10 mg/day to 100 mg bid) in phase 1 and 100 mg/day in phase 2
– Molecular profiling of tumour tissue and blood was performed
• All patients had tissue samples collected before enrolment and tissue collection was
encouraged on PD; tumour tissue was analysed with a ROS1 kinase domain mutation-
focused NGS panel
• Blood samples were collected at screening, at the beginning of cycle 3, and at the end-
of-treatment visit for circulating-free DNA (cfDNA) analysis using an NGS panel or
digital PCR
Solomon BJ, et al. Ann Oncol 2018;29(suppl 5):Abstr 1380PD
1380PD: Efficacy of lorlatinib in patients (pts) with ROS1-positive advanced
non-small cell lung cancer (NSCLC) and ROS1 kinase domain mutations
– Solomon BJ, et al
• Key results
• Conclusions
– ROS1 kinase domain mutations occurred in 10–14% of samples
– In patients with ROS1 kinase domain resistance mutations, lorlatinib exhibited
some anti-tumour activitySolomon BJ, et al. Ann Oncol 2018;29(suppl 5):Abstr 1380PD
ORR by presence of ROS1 mutations
Percentage change in tumour size from baseline
in patients with ≥1 ROS1 kinase domain mutation
ROS1 TKI-naïve
(n=17)
Prior crizotinib
(n=36)*
Prior non-
crizotinib TKI
or ≥2 TKIs
(n=5)
No
mutation
(n=17)
≥1
mutation
(n=0)
No
mutation
(n=27)
≥1
mutation
(n=8)
No
mutation
(n=4)
≥1
mutation
(n=1)
Best overall response, n (%)
CR 2 (11.8) – 1 (3.7) 0 0 0
PR 9 (52.9) – 8 (29.6) 2 ( 25.0) 0 0
SD 5 (29.4) – 8 (29.6) 5 (62.5) 3 (75.0) 1 (100)
PD 1 (5.9) – 3 (11.1) 1 (12.5) 1 (25.0) 0
Indeterminate 0 – 7 (25.9) 0 0 0
Responders, n (%) 11 (64.7) – 9 (33.3) 2 (25.0) 0 0
*One patient had a non-analysable or uninformative sample-100
-80
-60
-40
-20
0
20
40
60
80
100
Best perc
enta
ge c
hange fro
m b
aselin
e
Partial response
Stable disease
Progressive disease
Best overall response
ROS1 kinase domain mutation in:
cfDNA
Tumour tissue
Both cfDNA and tumour tissue
1381PD Gefitinib with or without pemetrexed in nonsquamous non-small cell
lung cancer with EGFR mutation: Final overall survival results from a
randomized phase II study – Chih-Hsin Yang J, et al
• Study objective
– To investigate the efficacy and safety of pemetrexed + gefitinib vs. gefitinib in
non-squamous NSCLC with EGFR mutations
Chih-Hsin Yang J et al. Ann Oncol 2018;29(suppl 5):abstr 1381PD
Key patient inclusion criteria
• Stage IV or recurrent non-squamous
NSCLC
• Activating EGFR mutations
• East Asian ≥18 years (≥20 years in Japan
and Taiwan)
• No prior systemic therapy for stage IV or
recurrent NSCLC
• ECOG PS 0–1
(n=191)
Gefitinib 250 mg/day
(n=65)
Pemetrexed 500 mg/m2 q3w
+ gefitinib 250 mg/day
(n=126)
Primary endpoint
• PFS
Secondary endpoints
• OS, time to progressive disease, tumour response rates,
DoR, QoL, biomarker analysis, safety
R
2:1
1381PD Gefitinib with or without pemetrexed in nonsquamous non-small cell
lung cancer with EGFR mutation: Final overall survival results from a
randomized phase II study – Chih-Hsin Yang J, et al
• Key results
– 36 (28.6%) patients had TEAEs in the pemetrexed + gefitinib group and
7 (10.8%) in gefitinib group
• Conclusion
– In patients with EGFR+ advanced NSCLC pemetrexed + gefitinib significantly
prolonged PFS, with a numerically longer, but not statistically significant,
improvement in OSChih-Hsin Yang J et al. Ann Oncol 2018;29(suppl 5):abstr 1381PD
Updated PFSOS
Time, months
Pro
babili
ty
1.0
0.8
0.6
0.4
0.2
0.0
0
126
65
6
118
64
12
106
53
18
92
45
24
79
36
30
66
27
36
58
26
42
51
19
48
43
15
54
30
8
60
3
2
66
1
0
72
0
0
No.at risk
P+G
G
Median OS, months (95%CI)43.4 months (33.4, 50.8)
36.8 months (26.7, 42.6)
Pemetrexed + gefitinib
Gefitinib
Adjusted HR 0.77 (95%CI 0.5, 1.2)
1-sided p=0.105
Time, months
Pro
babili
ty
1.0
0.8
0.6
0.4
0.2
0.0
0
126
65
6
98
51
12
70
29
18
50
18
24
29
9
30
19
6
36
14
4
42
12
2
48
7
2
54
5
1
60
0
0
No.at risk
P+G
G
Median PFS, months (95%CI)
16.2 months (12.6, 18.7)
11.1 months (9.7, 13.8)
Pemetrexed + gefitinib
Gefitinib
Adjusted HR 0.67 (95%CI 0.5, 0.9)
1-sided p=0.009
1382PD: Phase III study of gefitinib (G) versus gefitinib+carboplatin+pemetrexed
(GCP) as 1st-line treatment for patients (pts) with advanced non-small cell lung
cancer (NSCLC) with EGFR mutations (NEJ009) – Seike M, et al
• Study objective
– To investigate the efficacy and safety of gefitinib + carboplatin + pemetrexed vs.
gefitinib in patients with non-squamous NSCLC
Seike M, et al. Ann Oncol 2018;29(suppl 5):Abstr 1382PD
Primary endpoints
• PFS, PFS2, OS
Secondary endpoints
• ORR, safety, QoL
Gefitinib +
pemetrexed
q3w
Platinum-
based regimen
Stratification
• Sex
• EGFR mutation
• Smoking history
Key patient inclusion criteria
• Treatment naïve patients
with non-squamous IIIB/IV
NSCLC
• EGFR+
• PS 0–1
(n=345) Gefitinib 250 mg/day
Gefitinib 250 mg/day +
carboplatin AUC6 +
pemetrexed 500 mg/m2
R
1:1
Induction phase Maintenance phase
1382PD: Phase III study of gefitinib (G) versus gefitinib+carboplatin+pemetrexed
(GCP) as 1st-line treatment for patients (pts) with advanced non-small cell lung
cancer (NSCLC) with EGFR mutations (NEJ009) – Seike M, et al
• Results
• Conclusions
– PFS and OS were significantly improved in patients treated with combination
therapy of gefitinib + carboplatin + pemetrexed
– There was no difference in PFS2
Seike M, et al. Ann Oncol 2018;29(suppl 5):Abstr 1382PD
PFS
Gefitinib Gefitinib + carb + pem
Median PFS, months (95%CI) 11.2 (9.0, 13.4) 20.9 (18.0, 24.0)
HR (95%CI); p-value 0.490 (0.388, 0.620); <0.001
Gefitinib Gefitinib + carb + pem
mOS, months (95% CI) 38.8 (31.1, 47.3) 50.9 (41.8, 62.5)
HR (95%CI); p-value 0.72 (0.58, 0.95); 0.02
Updated OS
Overa
ll surv
ival, %
Time, months
100
80
60
40
20
0
0
172
170
12
153
162
24
115
131
36
86
106
48
62
77
60
26
29
No. at risk
Gefitinib
Gef + carb + pem
Pro
gre
ssio
n-f
ree s
urv
ival, %
Time, months
100
80
60
40
20
0
0
172
169
12
78
123
24
29
68
36
11
37
48
2
10
60
0
2
No. at risk
Gefitinib
Gef + carb + pem
1385PD: A randomised phase III trial evaluating the addition of denosumab to
standard first-line treatment in advanced NSCLC – the ETOP and EORTC
SPLENDOUR trial – Peters S, et al
• Study objective
– To investigate the efficacy of denosumab as an add-on to standard 1L doublet
chemotherapy + BSC in patients with NSCLC in the SPLENDOUR study
Peters S, et al. Ann Oncol 2018;29(suppl 5):Abstr 1385PD
Primary endpoint
• OS
Secondary endpoints
• PFS, OS by bone metastases, safety
Stratification
• Bone metastases
• PS
• Histology
• Region
Key patient inclusion criteria
• Stage IV NSCLC
(n=514)
Chemotherapy (4–6 cycles) + BSC*
(n=259)
Denosumab 120 mg every 3–4 weeks
+ chemotherapy (4–6 cycles)
(n=255)
*Zoledronic acid in case of skeletal involvement
R
1:1
1385PD: A randomised phase III trial evaluating the addition of denosumab to
standard first-line treatment in advanced NSCLC – the ETOP and EORTC
SPLENDOUR trial – Peters S, et al
• Key results
Peters S, et al. Ann Oncol 2018;29(suppl 5):Abstr 1385PD
Non-parametric Cox model
Treatment
Events/
patients
Median, years
(95%CI)
1 year, %
(95%CI)
HR
(95%CI)
p-value
(Score test)
Denosumab 177/2580.68
(0.62, 0.87)
40.2
(33.8, 46.5)
0.96
(0.78, 1.18)
BSC 178/2550.73
(0.63, 0.92)
40.2
(33.8, 46.5)1.00 0.689
OS PFS
Non-parametric Cox model
Treatment
Events/
patient
Median, years
(95%CI)
1 year, %
(95%CI)
HR
(95%CI)
p-value
(Score test)
Denosumab 228/2590.39
(0.35, 0.44)
13.1
(9.1, 17.9)
0.97
(0.81, 1.17)
BSC 227/2540.39
(0.34, 0.44)
9.3
(6.0, 13.6)1.00 0.777
OS
, %
100
80
60
40
20
00 2 3 41
29
23
2
0
83
82
259
255
Years
PF
S, %
100
80
60
40
20
00 20 28 3612
6
5
4
2
29
19
259
254
Months
4 24 3216
5
4
0
1
13
10
140
138
8
55
50
Denosumab
BSC
Denosumab
BSC
No. at risk
Denosumab
BSC
No. at risk
Denosumab
BSC
1385PD: A randomised phase III trial evaluating the addition of denosumab to
standard first-line treatment in advanced NSCLC – the ETOP and EORTC
SPLENDOUR trial – Peters S, et al
• Key results (cont.)
• Conclusions
– Denosumab added to 1L platinum-based chemotherapy did not improve OS
– There were no safety concerns with denosumab
Peters S, et al. Ann Oncol 2018;29(suppl 5):Abstr 1385PD
Non-parametric Cox model
Treatment
Events/
patients
Median, years
(95%CI)
1 year, %
(95%CI)
HR
(95%CI)
p value
(Score test)
Denosumab 98/1380.62
(0.46, 0.73)
34.4
(26.1, 43.0)
1.03
(0.78, 1.37)
BSC 98/1370.61
(0.51, 0.82)
35.8
(27.5, 44.2)1.00 0.816
OS
Bone metastases
OS
No bone metastases
Non-parametric Cox model
Treatment
Events/
patients
Median (years)
(95%CI)
1 year, %
(95%CI)
Hazard Ratio
(95%CI)
P-Value
(Score test)
Denosumab 79/1210.89
(0.67, 1.35)
46.9
(37.2, 55.9)
0.89
(0.65, 1.22)
BSC 80/1180.92
(0.71, 1.05)
45.4
(35.7, 54.6)1.00 0.483
OS
, %
100
80
60
40
20
00 20 28 4012
20
15
14
7
36
41
N
138
137
Months
4 24 3216
17
13
5
3
27
25
87
95
8
50
53
36
2
0
OS
, %
100
80
60
40
20
00 20 28 3612
19
14
7
6
47
41
N
121
118
Months
4 24 3216
12
10
2
2
35
24
95
87
8
65
66
Denosumab
BSCDenosumab
BSC
No. at risk
Denosumab
BSC
No. at risk
Denosumab
BSC
Advanced NSCLCNot radically treatable stage III and stage IV
Later lines
LBA63: Long-term survival in patients (pts) with advanced NSCLC in the
KEYNOTE-010 study overall and in pts who completed 2 years of
pembrolizumab (pembro) – Herbst RS, et al
• Study objective
– Long-term follow-up of KEYNOTE-010 investigating pembrolizumab vs.
docetaxel in patients with advanced NSCLC and PD-L1 TPS ≥1% who had
progressed after platinum-containing chemotherapy
Herbst RS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA63
Endpoints in TPS ≥50%
and ≥1% populations
• OS, PFS
• ORR, DoR, safety
Stratification
• ECOG PS (0 vs. 1)
• Region (East Asia vs. non-East Asia)
• PD-L1 status (TPS ≥50% vs. 1–49%)
Pembrolizumab 10 mg/kg q3w
for 24 months
R
1:1:1
Docetaxel 75 mg/m2 q3w
Pembrolizumab 2 mg/kg q3w
for 24 monthsKey patient inclusion criteria
• Advanced NSCLC
• PD-L1 TPS ≥1%
• Progression after ≥1 line of
chemotherapy
• No active brain metastases
LBA63: Long-term survival in patients (pts) with advanced NSCLC in the
KEYNOTE-010 study overall and in pts who completed 2 years of
pembrolizumab (pembro) – Herbst RS, et al
• Key results
Herbst RS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA63
Ove
rall
su
rviv
al, %
100
80
60
40
20
00
290
152
5
229
97
10
178
58
15
149
39
20
131
29
25
115
23
35
94
18
40
50
10
45
26
8
50
1
1
55
0
0
60
0
0
30
101
21
Time, months
35%
13%
N
Events,
n (%)
Median OS,
mo (95%CI)
HR (95%CI);
p-value
Pembrolizumab 290 199 (69) 16.9 (12.3, 21.4)0.53 (0.42, 0.66);
<0.00001Docetaxel 152 127 (84) 8.2 (6.4, 9.8)
PD-L1 TPS ≥50% population
Ove
rall
su
rviv
al, %
100
80
60
40
20
00
690
343
5
523
226
10
374
135
15
295
90
20
248
57
25
211
44
35
151
35
40
86
20
45
45
13
50
5
2
55
0
0
60
0
0
30
171
40
Time, months
23%
11%
N
Events,
n (%)
Median OS,
mo (95%CI)
HR (95%CI);
p-value
Pembrolizumab 690 548 (79) 11.8 (10.4, 13.1)0.69 (0.60, 0.80);
<0.00001Docetaxel 343 295 (86) 8.4 (7.6, 9.5)
PD-L1 TPS ≥1% population
OS
No. at risk
Pembro
Docetaxel
No. at risk
Pembro
Docetaxel
LBA63: Long-term survival in patients (pts) with advanced NSCLC in the
KEYNOTE-010 study overall and in pts who completed 2 years of
pembrolizumab (pembro) – Herbst RS, et al
• Key results (cont.)
– Overall, median treatment duration was 3.5 months (range 0.03–31.7) in the
pembrolizumab group (n=682) and 2.0 months (range 0.03–26.4) in the docetaxel
group (n=309)
– 79 patients completed 35 cycles or 2 years of pembrolizumab with a median
follow-up of 43.4 months (range 35.7–49.8)
• 75/79 (95%) patients had a CR or PR
– 48/75 (64%) patients had ongoing response, median DoR NR (range 4–46+ months)
• Median OS was NR (95%CI NR, NR)
– The Kaplan-Meier estimate of 36-month OS rate was 98.7% (95%CI 91.2, 99.8)
• 25/79 (32%) patients had PD after stopping 35 cycles or 2 years of pembrolizumab
– In 14 patients who received a second course of pembrolizumab after 35 cycles or
2 years of treatment and subsequent PD, 6 (43%) had PR and 5 (36%) had SD
• Conclusions
– In patients with PD-L1-expressing advanced NSCLC, pembrolizumab continued
to prolong OS compared with docetaxel
– In patients who completed 2 years of pembrolizumab AEs were manageable and
responses were durable Herbst RS, et al. Ann Oncol 2018;29(suppl 5):Abstr LBA63
1378O: ARCTIC: durvalumab + tremelimumab and durvalumab monotherapy vs
SoC in ≥3L advanced NSCLC treatment – Kowalski DM, et al
• Study objective
– To investigate the efficacy and safety of durvalumab vs. SoC and the combination of
durvalumab + tremelimumab vs. SoC in subgroups based on PD-L1 expression (≥25% or
<25%) in the ARCTIC study
Kowalski DM, et al. Ann Oncol 2018;29(suppl 5):Abstr 1378O
Stratification
• Planned SoC, histology
Study A
PD-L1 TC
≥25%
(n=126)
Study B
PD-L1 TC
<25%
(n=469)
R
1:1 SoC*
(n=64)
Durvalumab 10 mg/kg q2w for up to 12 mo
(n=62)
Key patient inclusion criteria
• Stage IIIB/IV NSCLC
• ≥2 prior treatments
• Immunotherapy-naïve
• EGFR/ALK wild-type
• WHO PS 0/1 SoC*
(n=118)
Durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w for 12 weeks then durvalumab
10 mg/kg for 34 weeks (n=174)
Tremelimumab 10 mg/kg q4w for 24 weeks
then q12w for 24 weeks (n=60)
R
3:2:2:1
*Erlotinib, gemcitabine, or vinorelbine
Durvalumab 10 mg/kg q2w for up to 12 mo
(n=117)
Primary endpoint
• OS, PFS (investigator assessed
Secondary endpoints
• 1-year OS and PFS rates, ORR, safety
1378O: ARCTIC: durvalumab + tremelimumab and durvalumab monotherapy vs
SoC in ≥3L advanced NSCLC treatment – Kowalski DM, et al
• Key results
Kowalski DM, et al. Ann Oncol 2018;29(suppl 5):Abstr 1378O
Durvalumab
(n=62)
SoC
(n=64)
Events, n (%) 48 (77.4) 55 (85.9)
Median OS,
months (95%CI)
11.7
(8.2, 17.4)
6.8
(4.9, 10.2)
HR (95%CI) 0.63 (0.42, 0.93)Pro
babili
ty o
f O
S
Time from randomisation, months
1.0
0.8
0.6
0.4
0.2
0.0
0
62
64
3
53
45
6
45
35
9
37
27
No. at risk
Durvalumab
SoC
Durvalumab
SoC
12
30
19
15
25
15
18
21
12
21
18
10
24
16
8
27
6
4
30
3
0
33
0
OS (PD-L1 TC ≥25%)
31.3%
49.3%
Durvalumab
(n=62)
SoC
(n=64)
Events, n (%) 58 (93.5) 58 (90.6)
Median PFS,
months (95%CI)
3.8
(1.9, 5.6)
2.2
(1.9, 3.7)
HR (95%CI) 0.71 (0.49, 1.04)
Pro
babili
ty o
f P
FS
Time from randomisation, months
1.0
0.8
0.6
0.4
0.2
0.0
0
62
64
3
34
25
6
22
14
9
18
10
No. at risk
Durvalumab
SoC
Durvalumab
SoC
12
12
5
15
10
2
18
7
2
21
5
2
24
5
1
27
1
0
30
0
0
33
PFS (PD-L1 TC ≥25%)
9.9%
19.4%
Study A
1378O: ARCTIC: durvalumab + tremelimumab and durvalumab monotherapy vs
SoC in ≥3L advanced NSCLC treatment – Kowalski DM, et al
• Key results (cont.)
• Conclusions
– Clinically meaningful improvement in OS was seen with durvalumab vs. SoC in
the PD-L1 TC ≥25% subgroup
– Combination therapy led to non-significant improvement in OS vs. SoC in PD-L1
TC <25% subgroupKowalski DM, et al. Ann Oncol 2018;29(suppl 5):Abstr 1378O
Pro
babili
ty o
f O
S
Time from randomisation, months
1.0
0.8
0.6
0.4
0.2
0.0
0
174
118
3
137
97
6
111
70
9
93
55
No. at risk
D + T
SoC
Durvalumab + tremelimumab
SoC
12
82
44
15
67
35
18
56
27
21
33
14
24
21
6
27
7
1
30
0
0
33
0
0
OS (PD-L1 TC <25%)
38.8%
49.5%Durvalumab + tremelimumab
SoC
Pro
babili
ty o
f O
S
Time from randomisation, months
0.8
0.6
0.4
0.2
0.0
0
174
118
3
90
51
6
49
25
9
41
13
No. at risk
D + T
SoC
12
31
6
15
23
3
18
17
3
21
11
1
24
9
0
27
1
0
30
0
0
8.0%20.6%
D + T (n=174) SoC (n=118)
Events, n (%) 118 (67.8) 90 (76.3)
mOS, months (95%CI) 11.5 (8.7, 14.1) 8.7 (6.5, 11.7)
HR (95%CI) 0.80 (0.61, 1.05), p=0.109
D + T (n=174) SoC (n=118)
Events, n (%) 146 (83.9) 92 (78.0)
mPFS, months (95%CI) 3.5 (2.3, 4.6) 3.5 (1.9, 3.9)
HR (95%CI) 0.77 (0.59, 1.01), p=0.056
PFS (PD-L1 TC <25%)Study B1.0
Other malignancies
SCLC, mesothelioma and thymic epithelial tumours
1664O: A randomized non-comparative phase II study of anti–PD-L1
atezolizumab or chemotherapy as second-line therapy in patients with small
cell lung cancer: results from the IFCT-1603 Trial – Pujol J, et al
• Study objective
– To investigate the activity of atezolizumab as systemic therapy in patients with
SCLC who have progressed after 1L platinum-based chemotherapy
Pujol J, et al. Ann Oncol 2018;29(suppl 5):Abstr 1664O
Primary endpoint
• ORR at 6 weeks (investigator assessed)
R
2:1
PD
PD
Stratification
• Sensitive vs. refractory disease
• PS (0–1 vs. 2)
• Limited vs. extensive disease
• Gender
Key patient inclusion criteria
• ED or LD SCLC
• Progressive disease after
1L chemotherapy
• No brain metastases
• PS 0–2
(n=73)
Chemotherapy:
topotecan (oral or IV) q3w or
carboplatin-etoposide q3w*
(n=24)
Atezolizumab 1200 mg q3w
(n=49)
*Maximum 6 cycles
1664O: A randomized non-comparative phase II study of anti–PD-L1
atezolizumab or chemotherapy as second-line therapy in patients with small
cell lung cancer: results from the IFCT-1603 Trial – Pujol J, et al
• Key results
Pujol J, et al. Ann Oncol 2018;29(suppl 5):Abstr 1664O
Atezolizumab
(n=43)
Chemotherapy
(n=20)
Total
(n=64)
ORR at 6 weeks, n (%)
[95%CI]
1 (2.3)
[0.0, 6.8]
2 (10)
[0.0, 23.1]
3 (4.8)
[0.0, 9.9]
DCR, n (%)
[95%CI]
9 (20.9)
[8.8, 33.1]
13 (65)
[44.1, 85.9]
22 (34.9)
[23.1, 46.7]
Progression, n (%)
[95%CI]
30 (69.8)
[56.0, 83.5]
6 (30)
[9.9, 50.1]
36 (57.1)
[44.9, 69.4]
Not done/not evaluable,
n (%) [95%CI]
4 (9.3)
[0.6, 18.0]
1 (5.0)
[0.0, 14.6]
5 (7.9)
[1.3, 14.6]
1664O: A randomized non-comparative phase II study of anti–PD-L1
atezolizumab or chemotherapy as second-line therapy in patients with small
cell lung cancer: results from the IFCT-1603 Trial – Pujol J, et al
• Key results (cont.)
• Conclusions
– In pre-treated patients with progressive SCLC, the efficacy of atezolizumab was
inferior to chemotherapy
– ORR at 6 weeks with atezolizumab monotherapy was 2.3% and median PFS
was 1.4 months
– Therefore, the planned phase 3 portion of the study was not activated
Pujol J, et al. Ann Oncol 2018;29(suppl 5):Abstr 1664O
HR (adjusted) atezolizumab group = 2.26 (95%CI 1.30, 3.93); p=0.004
PFS (ITT population)
Time, months0 1 2 3 5 6 7 8 94
Median follow-up: 13.7 months (95%CI 12.7, NR)
Chemotherapy (n=24): 4.3 (1.5, 5.9); 21 events, 3 censored
Atezolizumab (n=49): 1.4 (1.2, 1.5); 46 events, 3 censored
6-month PFS rate for atezolizumab group: 6.3% [0.0, 13.1]
Pro
gre
ssio
n-f
ree s
urv
ival
1.0
0.8
0.6
0.4
0.2
0
Median PFS, months (95%CI)
1665PD: Preliminary efficacy of durvalumab plus tremelimumab in platinum-
refractory/resistant EDSCLC from arm A of the phase II BALTIC study
– Bondarenko I, et al
• Study objective
– To determine the efficacy and safety of durvalumab + tremelimumab in patients
from the BALTIC study with extensive-disease (ED) SCLC who have platinum-
refractory or -resistant disease
Primary endpoint
• ORR
Secondary endpoints
• DCR at 12 weeks, DoR, TTR, PFS, OS,
safety
Cohort A:
Durvalumab 1500 mg +
tremelimumab 75 mg q4w
for up to 4 months, then
durvalumab 1500 mg q4w
(n=10)
Interim
analysis*
Key patient inclusion criteria
• ED-SCLC
• Refractory or resistant to 1L
chemotherapy
• Life expectancy ≥8 weeks
• No prior exposure to immunotherapy
• WHO/ECOG PS 0–1
Bondarenko I, et al. Ann Oncol 2018;29(suppl 5):Abstr 1665PD*Interim ORR analysis followed by expansion stage with n=20
1665PD: Preliminary efficacy of durvalumab plus tremelimumab in platinum-
refractory/resistant EDSCLC from arm A of the phase II BALTIC study
– Bondarenko I, et al
• Key results
– Confirmed ORR was 9.5% (95%CI 1.2, 30.4) with PR in 2 patients
– Median PFS was 1.9 months (95%CI 1.8, 4.3)
– Median OS was 6.0 months (95%CI 1.9, 12.0)
• Conclusion
– In patients with platinum-refractory ED-SCLC, durvalumab + tremelimumab
showed promising activity, with a safety profile consistent with previous reports
Bondarenko I, et al. Ann Oncol 2018;29(suppl 5):Abstr 1665PD
Maximum percentage change in target lesion size
Be
st ch
an
ge
fro
m b
ase
line
in t
arg
et le
sio
n s
ize
, %
100
80
60
40
20
–20
–40
–60
–80
–100
Non-response
Response
0
1667PD: Impact of early prophylactic cranial irradiation with hippocampal
avoidance on neurocognitive function in patients with limited disease small-cell
lung cancer. A multicenter phase II trial (SAKK 15/12) – Vees H, et al
• Study objective
– To investigate the neurocognitive function (NCF) in patients with limited-disease
SCLC treated with prophylactic cranial irradiation (PCI) concomitant with
chemotherapy and thoracic radiotherapy (tRT) in the SAKK 15/12 study
• Methods
– Patients received hippocampal avoidance PCI at the start of the 2nd cycle of
chemotherapy (cisplatin or carboplatin and etoposide) and tRT (total of 6 cycles
of chemotherapy)
– NCF was tested prior to PCI and at weeks 11, 29 and 53
• Memory was assessed using Hopkins Verbal Learning Test Revised (HVLT-R);
language and verbal fluency was assessed using Controlled Oral Word Association
Test (COWAT); visual search, scanning, speed of processing and executive function
was assessed using Trail Making Tests A and B (TMT A&B)
– NCF decline was defined as a decrease of 1 SE of measurement in any test
• A rate of ≤30% in patients with no NCF decline was assumed unpromising and a rate of
≥50% in patients with no NCF decline was assumed promising
Vees H, et al. Ann Oncol 2018;29(suppl 5):Abstr 1667PD
1667PD: Impact of early prophylactic cranial irradiation with hippocampal
avoidance on neurocognitive function in patients with limited disease small-cell
lung cancer. A multicenter phase II trial (SAKK 15/12) – Vees H, et al
• Key result
– No brain metastases were observed during 6 months
– OS was 87% (95%CI 72, 94)
– Overall 7 patients died: 4 due to disease progression, 1 due to respiratory failure, 1 due to
haemorrhage and 1 for unknown reason
– The most common grade ≥3 AEs were: anaemia (21%), febrile neutropenia (19%) and
fatigue (14%)
• Conclusion
– The proportion of patients with no decline in NCF at 6 months is similar to that in those
receiving sequential PCI
Vees H, et al. Ann Oncol 2018;29(suppl 5):Abstr 1667PD
Deterioration of NCF by cognitive test
1310
79 9 9
25
0
5
10
15
20
25
30
HVLT-R totalrecall
HVLT-Rdelayed recall
HVLT-R RDI COWAT TMT-A TMT-B Deteriorationin at least one
test
Deterioration of NCF n (%) 90%CI
No 13 (34.2) 21.6, 48.8
Yes 25 (65.8)
Nu
mb
er
of p
atie
ntsDeterioration of NCF at 6 months