Maximising Clinical Benefit from TKIs in the Treatment of Advanced NSCLC 2017 WCLC- PACIFICO Yokohama Convention Center 16 October, 2017 BI symposium
Maximising Clinical Benefit from TKIs in the Treatment of
Advanced NSCLC
2017 WCLC- PACIFICO Yokohama Convention Center
16 October, 2017
BI symposium
Meeting Welcome and Introductions
2017 WCLC- PACIFICO Yokohama Convention Center
Tetsuya Mitsudomi, MD, PhD
Kindai University Faculty of Medicine
Osaka-Sayama, Japan
3
Faculty Disclosure
• Honoraria and Advisory boards: AstraZeneca, Boehringer Ingelheim, Chugai,
Pfizer, MSD, and Ono
• Grant support: Boehringer Ingelheim, Chugai, Pfizer, and Ono.
4
Agenda
Time Topic Speaker
12:45 – 12:50 Meeting Welcome and Introductions Tetsuya Mitsudomi
(Japan)
12:50 – 13:10 Emerging Algorithm for Optimal Sequencing of EGFR TKIs in EGFR Mutation-
Positive NSCLC
Keunchil Park
(S. Korea)
13:10 – 13:30 Efficacy of EGFR TKIs in NSCLC Patients with Uncommon EGFR Mutations Terufumi Kato
(Japan)
13:30 – 13:50 Considerations for Choosing TKIs for Squamous NSCLC in the Era of
Immunotherapy: Which Patients Could Benefit?
Barbara Melosky
(Canada)
13:50 – 14:10
Panel Discussion
Carrying the Data into the Clinic: TKI Sequencing Decisions for EGFR Mutation-
Positive NSCLC Patients
All Faculty
Moderator:
Tetsuya Mitsudomi
14:10 – 14:15 Meeting Close Tetsuya Mitsudomi
5
Faculty
Chair: Tetsuya Mitsudomi, MD, PhD
Kindai University Faculty of Medicine
Osaka-Sayama, Japan
Terufumi Kato, MD
Kanagawa Cardiovascular and
Respiratory Center
Tokyo, Japan
Keunchil Park, MD, PhD
Samsung Medical Center,
Sungkyunkwan University School of Medicine
Seoul, Korea
Barbara Melosky, MD, FRCPC
University of British Columbia,
British Columbia Cancer Agency
Vancouver, BC
Emerging Algorithm for Optimal Sequencing of EGFR TKIs in
EGFR Mutation‒Positive NSCLC 2017 WCLC- PACIFICO Yokohama Convention Center
Keunchil Park, MD, PhD
Samsung Medical Center,
Sungkyunkwan University School of Medicine
BI symposium
7
Faculty Disclosure
• Consulting or Advisory Role: Astellas Pharma; AstraZeneca; Boehringer
Ingelheim; Clovis Oncology; Hanmi; Kyowa Hakko Kirin; Lilly; Novartis; Ono
Pharmaceutical; Roche
• Speakers' Bureau: Boehringer Ingelheim
• Research Funding: AstraZeneca
8
Key Factors in First-line EGFR
TKI Selection
Sequence makes survival
Not all TKIs are equal
Efficacy Drug-drug
interactions
Adverse event profile
9
Key Factors in First-line EGFR
TKI Selection
Sequence makes survival
Not all TKIs are equal
Efficacy Drug-drug
interactions
Adverse event profile
10
The Family of EGFR TKIs
Liao et al. Curr Opin Oncol. 2015;27:94.
Wild-type EGFR
Intrinsic mutant EGFR
Acquired T790M EGFR
2nd-generation TKI
3rd-generation TKI
K K K K K K
K Kinase domain
Activity range
Activity
• Reversible binding to wild-type and mutant EGFR
• Inactive on T790M mutant
• Irreversible covalent binding to EGFR, ErbB2 and ErbB4 to inhibit
all ErbB Family signalling • Broader activity to overcome EGFR TKI‒resistant mutations
• Specificity for EGFR T790M mutant; EGFR
wild-type sparing • Irreversible covalent binding to mutant EGFR
EGFR inhibition
ErbB Family blockade
EGFR mutant‒specific inhibitor
1st-generation TKI Activity range Erlotinib
Gefitinib
Afatinib
Dacomitinib
Osimertinib
K
ErbB heterodimers (eg, Her2: ErbB3)
Range
11
Activity of First-, Second-, and Third-Generation EGFR
TKIs Against EGFR Mutations
Li et al. Oncogene. 2008;27:4702; Cross et al. Cancer Discov. 2014;4:1046; Hirano et al. Oncotarget. 2015;6:38789.
IC50 = half-maximal inhibitory concentration.
EGFR mutant: L858R, exon 19 del Wild-type EGFR T790M
Gefitinib Afatinib Osimertinib
EGFRm
EGFRm
EGFRm
Wild-type
Wild-type
Wild-type
T790M
T790M
100×
10×
1×
T790M
IC5
0 (
nM
)
12
Key Factors in First-line EGFR
TKI Selection
Sequence makes survival
Not all TKIs are equal
Efficacy Drug-drug
interactions
Adverse event profile
13
First- and Second-Generation EGFR TKIs Are Standard for
First-line Treatment of NSCLC With Common EGFR Mutations
• Better PFS vs platinum-based chemotherapy
Chen et al. Ann Oncol. 2013;24:1615; Gefitinib Summary of Product Characteristics 2010; Han et al. J Clin Oncol. 2012;30:1122; Maemondo et al. N Engl J Med.
2010;362:2380; Mok et al. N Engl J Med. 2009;361:947; Mitsudomi et al. Lancet Oncol. 2010;11:121; Rosell et al. Lancet Oncol. 2012;13:239; Sequist et al. J Clin Oncol.
2013;31:3327; Wu et al. Lancet Oncol. 2014;15:213; Wu et al. Ann Oncol. 2015;26:1883; Zhou et al. Lancet Oncol. 2011;8:735.
aPFS not reported for common mutations only.
NSCLC = non‒small cell lung cancer.
Gefitiniba Erlotinib Platinum-based chemotherapy
[VALUE] 11
13.1
9.2
10.8
9.7a
13.6
11
5.2 5.5 4.6
[VALUE] 5.4
[VALUE]a 6.9
5.6
Afatinib
month
s
EURTAC ENSURE OPTIMAL WJTOG NJE002 IPASS LL3 LL6 EURTAC ENSURE OPTIMAL WJTOG NJE002 IPASS LL3 LL6
14
First- and Second-Generation EGFR TKIs Are Not Equal:
Response Rate and PFS in LUX-Lung 7
LUX-Lung 7: Afatinib vs Gefitinib
Park et al. Lancet Oncol. 2016;17:577; Corral et al. ELCC 2017. Abstract 93PD.
P=0.002
73% 75%
69%
56%
66%
42%
0%
20%
40%
60%
80%
ITT Del19 L858R
Re
sp
on
se
ra
te (
%)
P=0.150 P=0.003
Gefitinib Afatinib P
FS
(%
)
Time (months)
160 142 112 94 67 47 34 27 21 13 6 3 1 0 0
159 132 106 83 52 22 14 9 7 5 3 3 1 1 0
Afatinib
Gefitinib
27%*
18%†
15%
100
80
60
40
20
0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42
8%
Afatinib
(n=160)
Gefitinib
(n=159)
Median, mo 11.0 10.9
HR (95% CI)
P value
0.73 (0.57-0.95)
P=0.017
15
First- and Second-Generation EGFR TKIs Are Not Equal:
PFS in ARCHER 1050
ARCHER 1050: Dacomitinib vs Gefitinib (excluding CNS metastases)
Mok et al. ASCO 2017. Abstract LBA9007.
CNS = central nervous system; ITT = intent-to-treat; CI, confidence interval.
PFS: Blinded Independent Review (ITT population)
Months
0
0
0
0
6
1
20
7
73
34 106
69
154
155
227
225
No. at risk:
Dacomitinib
Gefitinib
Pro
ba
bilit
y o
f P
FS
1.0
0.8
0.6
0.4
0.2
0.0
0 6 12 18 24 30 42 36
++ Censored
PFS rate
30.6% vs 9.6% Dacomitinib
Gefitinib
Dacomitinib
(n=227)
Gefitinib
(n=225)
Number of events, n (%) 136 (59.9%) 179 (79.6%)
Median PFS (95% CI) 14.7
(11.1-16.6)
9.2
(9.1-11.0)
HR (95% CI)
P value
0.59 (0.47-0.74)
P=0.0001
16
First and Third-Generation EGFR TKIs Are Not Equal:
PFS in FLAURA
Ramalingam et al. ESMO 2017. Abstract LBA2.
DCO: 12 Jun 2017.
Tick marks indicate censored data. aFor statistical significance, P<0.0015, determined by O’Brien planning approach, was required.
OS = overall survival; SoC = standard of care; NS = not significant; DCO = data cut -off.
FLAURA: Osimertinib vs Gefitinib or Erlotinib
Primary Endpoint: PFS (by Investigator Assessment)
Pro
ba
bilit
y o
f P
FS
Time from randomisation (months)
Osimertinib
Gefitinib or Erlotinib
1.0
0.8
0.6
0.4
0.2
0.0 0 3 6 9 12 15 18 21 24 27
279
277
No. at risk:
Osimertinib
SoC 262
239
233
197
210
152 178
107
139
78 71
37
26
10
4
2
0
0
Osimertinib Gefitinib
or Erlotinib
Median PFS,
months (95%
CI)
18.9
(15.2-21.4)
10.2
(9.6-11.1)
HR (95% CI)
P value
0.46 (0.37-0.57)
P<0.0001
17
Key Factors in First-line EGFR
TKI Selection
Sequence makes survival
Not all TKIs are equal
Efficacy Drug-drug
interactions
Adverse event profile
18
Safety
Second- or Third-Generation TKIs vs First-Generation TKIs
1. Park et al. Lancet Oncol. 2016;17:577; 2. Paz-Ares et al. Ann Oncol. 2017;28:270; 3. Mok et al. ASCO 2017. Abstract LBA9007; 4. Ramalingam et al. ESMO 2017. Abstract
LBA2.
LUX-Lung 71,2 ARCHER 10503 FLAURA4
Afatinib
(n=160)
Gefitinib
(n=159)
Dacomitinib
(n=227)
Gefitinib
(n=225)
Osimertinib
(n=279)
Treatment
discontinuation
rate
6.3% 6.3% 9.7% 6.6% 13.0%
(any)
Most common
grade ≥3 AEs
Diarrhoea: 12%
Rash/acne: 9%
Liver enzyme
elevation: 9%
Rash/acne: 3%
Acne: 14%
Diarrhoea: 9%
Paronychia: 8%
Liver enzyme
elevation: 9%
Paronychia: 1%
Diarrhoea: 2%
Decreased
appetite: 3%
19
Dose Reduction of Afatinib Reduced Drug-Related AEs
Without Compromising Efficacy
Hirsch V, et al. ASCO 2016 poster presentation: 369.
PFS = progression-free survival; HR = hazard ratio; CI = confidence interval.
Treatment-Related AEs in Patients Who
Had a Dose Reduction From 40 mg (n=63)
100.0 95.2
81.0
60.3
28.6
[VALUE]
25.4 [VALUE] 7.9 3.2 0
20
40
60
80
100
Any Diarrhoea Rash/acne Stomatitis Nail effect
pa
tie
nts
(%
)
90.5
61.9 52.4
27.0 33.3
23.8 9.5 3.2 3.2 0.0
0
20
40
60
80
100
Any Diarrhoea Rash/acne Stomatitis Nail effect
pa
tie
nts
(%
)
Be
fore
re
du
cti
on
(≥40 m
g),
Aft
er
red
ucti
on
(<40 m
g),
PFS in Patients Who Received a Dose Reduction
Within the First 6 Months of Treatment
Est
ima
ted
PF
S p
rob
ab
ilit
y
1.0
0.8
0.6
0.4
0.2
0
0 3 6 9 12 15 18 21 24 27 30 33 36 39
Months
45 34 28 22 15 11 10 9 7 3 1 0 0 47
113 97 78 66 45 32 23 17 12 6 3 2 1 0
No. at risk:
<40 mg
≥40 mg
<40 mg in
First 6 Months
(n=47)
≥40 mg for
First 6
Months
(n=113)
Median, mo 12.8 11.0
HR (95% CI)
P value
1.34 (0.90-2.00)
P=0.1440
All grade Grade ≥3
20
Key Factors in First-line EGFR
TKI Selection
Sequence makes survival
Not all TKIs are equal
Efficacy Drug-drug
interactions
Adverse event profile
21
DDIs of First-, Second-, and Third-Generation EGFR TKIs
Cross et al. Cancer Discov. 2014;4:1046; Li et al. Oncogene. 2008;27:4702; Peters et al. Cancer Treat Rev. 2014;40:917; TAGRISSO Prescribing Information. March 2017.
Enzymes Involved in the Metabolism of Oral EGFR TKIs
May Inhibit May Induce Drug
Metabolised by CYP Enzymes
3A4 3A5 2D6 1A1 1A2 1B1 2C8 2C9
Gefitinib +++ ++ +++ ++ + -
CYP2C19 (w)
CYP2D6 (w) UGT1A9, BRCP
Erlotinib +++ +++ + + ++ + + +
CYP3A4 (m)
CYP2C8 (m) CYP1A1 (s)
UGT1A1 (s)
CYP1A1
CYP1A2
Afatinib - - - - - - - - - -
Dacomitinib ++ ++ + CYP2D6 (s)
Osimertinib +++ +++ - - - - - - BCRP
CYP3A4
CYP1A2 CYP2C
DDI = drug-drug interaction; CYP = cytochrome P450 enzyme; BCRP = breast cancer resistance protein; UGT = UDP-glycosyltransferase.
22
Key Factors in First-line EGFR
TKI Selection
Sequence makes survival
Not all TKIs are equal
Efficacy Drug-drug
interactions
Adverse event profile
23
OS with Afatinib in EGFR-Mutant NSCLC
Yang et al. Lancet Oncol. 2015;16:141.
Common Mutations (del19/L858R) (n=307)
aOnly 6 patients in the afatinib arm w ere treated with osimertinib because of lack of availibility (trial recruitment w as from August 2009 to February 2011).
NSCLC = non‒small cell lung cancer.
0
0.2
0.4
0.6
0.8
1.0
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51
Months
197 188 101 90 58 9 203
104 98 92 40 35 26 5
No. at risk:
Af atinib
Cis/Pem
181
86
171
81
162
71
143
63
133
55
121
52
108
47
49
20
32
10
1
1
0
0
No. at risk:
Af atinib
Cis/Pem
Es
tim
ate
d O
S p
rob
ab
ilit
y
Afatinib
Cis/Pem
Common mutation
Afatiniba
(n=203)
Cis/Pem
(n=104)
Median, mo 31.6 28.2
HR (95% CI) 0.78 (0.58-1.06)
24
Molecular Mechanisms of Acquired Resistance to
First-/Second-Generation EGFR TKIs
Yu HA et al. Clin Cancer Res. 2013;19:2240.
• 155 EGFR mutant NSCLC,
acquired resistance after TKI
• Molecular analyses on
re-biopsy specimen
T790M
(60%)
Unknown (18%)
HER2 (8%)
MET amplification (3%)
Small cell+MET (1%)
Small cell (1%)
Small cell+T790M (2%)
MET+T790M (3%)
HER2 T790M (4%)
25
OS in Patients Treated With Third-Generation TKIs
Subsequently in LUX-Lung 7
Corral et al. ELCC 2017. Abstract 93PD.
NE = not estimable.
20%/17% who discontinued afatinib/gefitinib received third-generation TKIs (osimertinib, olmutinib,
rociletinib)
Months
Es
tim
ate
d O
S p
rob
ab
ilit
y
0.8
1.0
0.6
0.4
0.2
0
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57
30
26
No. at risk:
Afatinib
Gefitinib 30
26
30
25
30
25
30
25
30
24
29
23
29
23
29
23
29
22
28
22
28
22
26
20
21
17
17
17
14
10
8
4
1
1
0
0
Afatinib
(n=30)
Gefitinib
(n=26)
Median, mo NE 48.3
HR (95% CI)
P value
0.49 (0.20-1.19)
P=0.107
26
Treatment Sequences in EGFR-Mutant NSCLC After
First-line EGFR TKI
1st-/2nd-generation TKI
Osimertinib T790M +
T790M
-
Other
Chemotherapy 1st-/2nd-generation TKI
MET/HER2 inhibitor
Chemotherapy
Except if molecular target
Osimertinib Chemotherapy
Except if molecular target
NEED MATURE OS AND TREATMENT SEQUENCES FROM AURA3 and FLAURA (med PFS = 18.9 months)
27
Key Factors in First-line EGFR
TKI Selection
Sequence makes survival
Not all TKIs are equal
Efficacy Drug-drug
interactions
Adverse event profile
For more information about other BI events and collaborations, please visit www.inOncology.com
Efficacy of EGFR TKIs in Patients With NSCLC With Uncommon
EGFR Mutations 2017 WCLC- PACIFICO Yokohama Convention Center
Terufumi Kato, MD
Kanagawa Cancer Center,Yokohama, Japan
BI Symposium
30
Faculty Disclosure
• Honoraria: AstraZeneca; Boehringer Ingelheim; Chugai Pharma; Kyowa
Hakko Kirin; Lilly; Ono Pharmaceutical; Pfizer; Roche; Taiho Pharmaceutical
• Consulting or Advisory Role: AstraZeneca; Nippon Boehringer Ingelheim;
Ono Pharmaceutical
• Research Funding: Abbvie; Astellas Pharma; AstraZeneca; Bristol-Myers
Squibb; Chugai Pharma; Daiichi Sankyo; Kyowa Hakko Kirin; Lilly; Merck
Sharp & Dohme; Nippon Boehringer Ingelheim; PAREXEL; Pfizer; Quintiles;
Shionogi Pharma; Taiho Pharmaceutical; Takeda; Yakult Honsha
31
EGFR Mutations in NSCLC
Mitsudomi et al., Cancer Science, 2007
Mitsudomi et al., Cancer Science, 2007
EGF binding EGF binding TM Tyrosine kinase Autophosphorylation
Exon 2 5 7 13 16 17 18-21 22-24 28
68
8
72
8
72
9
76
1 7
62
82
3
82
4
87
5
Exon 18 (nucleotide binding loop) Exon 19 Exon 20
Exon 21 (activation loop)
Ex19Del L858R
G719X L861Q Ex20 Ins
32
Common or Uncommon/Non-classical (N=1,632)
Shen et al. Lung Cancer. 2017;110:56.
Single, uncommon/non-classical mutations
or insertion: 8%
Exon 21 single 1%
Exon 20 single 1% insertions 3%
Exon 19 single 0.4% Exon 18 single 3%
Uncommon/non-classical mutation with Del19/L858R: 6%
Complex uncommon/non-classical, without Del19 and L858R: 2%
Del19
(n=354) 42%
Ex21
L858R (n=356)
42%
33
• Irreversible second- and third-generation TKIs overcome resistance induced by
uncommon secondary mutations
In Vitro Activity of First-, Second-, and Third-Generation TKIs
Against Uncommon EGFR Mutations
Chiba M et al. BMC Cancer. 2017;17:281.
Gefitinib
Erlotinib
Afatinib
Dacomitinib
Osimertinib IC50 (
nM
)
10000
0
5
10
15
20
25
30
35
40
45
50
L858R L858R/L747S L858R/D761Y L858R/T854A L858R/T790M
34
In Vitro Activity of First-, Second-, and Third-Generation
TKIs Against Uncommon EGFR Mutations • In separate assays, first- and third-generation TKIs demonstrated reduced activity against cell lines harbouring
uncommon mutations, whereas the response to afatinib was similar across cell lines
1. Saxon et al. J Thorac Oncol. 2017;12:884; 2. Banno et al. Cancer Sci. 2016;107:1134.
TKI = tyrosine kinase inhibitor; IC50 = 50% inhibitory concentration.
1 1 1
20
2.5 3.6
32
3.5
20
0
10
20
30
40
IC50 r
ati
o r
ela
tiv
e
to L
85
8R
L861Q and S768I2
L858R L861Q S768I L858R L861Q S768I L858R L861Q S768I
Erlotinib Afatinib Osimertinib
125
100
75
50
25
0 0 0.001 10 1 0.1 0.01
µM
Ce
ll v
iab
ilit
y (%
)
Afatinib
Gefitinib
Osimertinib
125
100
75
50
25
0 0 0.001 10 1 0.1 0.01
µM
Ce
ll v
iab
ilit
y (%
)
L858M/L861Q1
L858R
Afatinib
Gefitinib
Osimertinib
L858M/L861Q
35
EGFR Exon 18 Mutations in Lung Cancer:
Molecular Predictors of Augmented Sensitivity to Afatinib as
Compared with First- or Third-Generation TKIs
• Among 1,402 EGFR mutations, Del19, L858R, and Ins20 were detected in 40%, 47%, and 4%, respectively.
Exon 18 mutations, including G719X, E709X, and Del18, were present in 3.2%
• Patients with lung cancers harbouring G719X exhibited higher response rate to afatinib (80%) than to 1G TKIs
(35%–56%)
Kobayashi Y et al. CCR 2015.
IC90s
of
EG
FR
-TK
Is
in T
ran
sfe
cte
d
Ba
/F3 C
ell
s (n
mo
l/L
)
104
103
102
101
100
10–1 Gefitinib Erlotinib Afatinib Dacomitinib AZD9291
882
187 213
7
9,350
884
215 167
6
>10,000
448*
2,717
69
1.7
0.7 0.9
0.3
>100
29 16
166
6
1.6
>1,000
3,078
400*
1.1
53 62
93
Del 18
E709K
G719A
Del 19
WT
Ctrough
Del 19 40% (n=563)
Ins 20 4% (n=63)
Others 5% (n=71)
Exon 18 3% (n=45)
L858R 47% (n=660)
G719A (n=22)
G719S (n=9)
G719C (n=8)
G719R (n=1)
G719V (n=1)
E709H + G719C (n=1)
Del E709_T710 ins D (n=3)
*
*
*
36
Case Report: Afatinib in a TKI-Pretreated Patient With
EGFR L858M/L861Q (in cis) • 62-year-old Caucasian female with extensive involvement of a poorly differentiated adenocarcinoma
• Worsening disease with 4 months of erlotinib and 4 months of chemotherapy
• Radiographic response 2 months after initiation of afatinib
• Remained on afatinib, with Grade 1 diarrhoea as her only side effect, for 10 months and continues treatment
Saxon et al. J Thorac Oncol. 2017;12:884.
37
Clinical Data in TKI-Pretreated Patients: Radiographic
Responses After Suboptimal Response to Other EGFR-TKIs
Peled et al. J Thorac Oncol. 2017;12:e81.
Patient With ex19del, T790M, and G724S
C797S
T790M
G724S
ex19del
TP53
Mar-15 Sep-15 Oct-15 Dec-15 Mar-16
2.9
0.1
0.3
6.5
19.5
24.2
33
23.6
33.7
7.8
23.7
15.1
39.6
2.6
45.7
60.1
Cell-free DNA tumor response. Cell-free DNA analysis of total somatic alteration burden detected over five time points and
the EGFR variant-specific results over time reflect responses to changes in matched therapy. TP53, tumor protein p53
Apr-14
Gefitinib
Jun-15
Osimertinib
Sep-15
Osimertinib + Afatinib
Dec-15
Pemetrexed
38
Clinical Data in TKI-Pretreated Patients: Best Response in Patients
With LMD Harbouring Uncommon Mutations
• 3/11 patients with leptomeningeal carcinoma treated with afatinib harboured an uncommon Exon 18
mutation (L719X)
• Median CSF concentration in all 11 patients was 2.88 nM (afatinib’s IC50 for EGFR being 0.5 nM).
PFS and OS in patients harbouring a G719X mutation were 5.6 months (2.0-10.0) and 7.0 months (5.6 ongoing to 13.0)
Tamiya et al. Anticancer Res. 2017;37:4177.
aTreatment continued after data cutoff; bCensored at data cutoff (patient still alive).
LMD = leptomeningeal disease; CSF = cerebrospinal f luid; PFS = progression-free survival; OS = overall survival; NE = Not evaluated; PR = partial response;
PD = progressive disease.
Plasma CSF
Best
Response PFS (Days) OS (Days)
1 146.9 NE PR 309 396
2 192.0 6.0 PD 61 212
3 767.6 0.8 PR 171a 171b
Concentration of Afatinib in Plasma and CSF, Penetration Rate, and Efficacy in Patients With EGFR Mutation-Positive NSCLC With LMD
Concentration (nM)
39
Clinical Data in TKI-Pretreated Patients:
Time to Treatment Failure With Afatinib • 66 uncommon mutations were reported (18.4% of all known EGFR mutations in the compassionate-use programme)
– Majority of patients (67%) received afatinib as third- or fourth-line treatment, with median treatment duration of 3.6 months
• No significant difference between median TTF for patients with uncommon/non-classical mutations (3.6 months) compared
with those with Del19 (4.6 months) or L858R (5.8 months) mutations
Heigener et al. Oncologist. 2015;20:1167.
TTF = time to treatment failure.
Distribution of the 60 Rare
EGFR Mutations (N=60)
Exon 18
substitution, 1, 2%
Exon 19
insertion/deletion, 2, 3%
Exon 19 substitution, 4,
7%
Exon 20 insertion, 3, 5%
T790M, 1, 2%
Exon 21 substitution, 4,
7%
Complex mutations
incl. T790M, 29
48%
G719X, 7,
11%
Complex
mutations, 9
15%
100
75
50
25
0 0 6 12 18 24 30
Months
Tre
atm
en
t p
rob
ab
ilit
y (
%) Del19
L858R
Uncommon
40
First-line Clinical Data: Retrospective Analysis of PFS in
57 Patients Treated With Afatinib or First-Generation TKIs • In all mutation groups analysed, the afatinib group
exhibited longer median PFS compared with first-generation TKIs
– Entire uncommon mutations cohort, except exon
20 insertionsa: 11.0 mo vs 3.6 mo
– G719X, S768I, or L861Q: 18.3 mo vs 2.6 mo
– Uncommon mutations with Del19 or L858R:
11.0 mo vs 8.2 mo
Del19+ 18G721D; Del19+ 19L732P; Del19+ 20L792P; Del19+
20S768I + 20V774M; Del19+ 21L858R + 21K860I; 21L858R + 18E709X; 21L858R + 20S768I; 21L858R + 20V786E; 21L858R
+ 20T790M; 21L858R + 20 insertion; 21L858R + 21L833Vl
21L858R + 21K860I; 21L858R + 18G719X +20 insertion
– Uncommon mutation alone or in combination with other
uncommon mutations: 18.3 mo vs 2.8 mo
18I715V; 18K716E; 18V717G; 18G719X; 19L747P;19
insertion; 20A763_Y764 insFQEA; 20S768I; 20G779F;
21L861Q; 18G719X+21L861Q; 18E709X + 18G719X;
18G719X +20S768I; 20T790 M+ 21L861Q; 21M825L +21R831C; 18V703L + 18L707W +18G719X; 18E709X +
18T710S + 18G719X; 19V742F + 19A743 V+ 20H773R
Shen et al. Lung Cancer. 2017;110:56.
CI = confidence interval. aexon 20 insertions (except A763_Y764 insFQEA).
No. at risk 1st TKI 30 12 8 4 2 0 0 0 2nd TKI 21 13 8 5 2 2 1 0
No. at risk 1st TKI 21 6 4 2 1 0 0 0 2nd TKI 13 8 3 3 1 1 0 0
Entire Uncommon Mutations Cohort,
Except Exon 20 Insertions
Uncommon Mutations With
Del19 or L858R
Uncommon Mutation Alone or in Combination
With Other Uncommon Mutations
G719X, S768I, or L861Q 100
90
80
70
60
50
40
30
20
10
0
PF
S (
%)
Months
0 5 10 15 20 25 30 35
Log rank P=0.03
100
90
80
70
60
50
40
30
20
10
0
PF
S (
%)
Months
0 5 10 15 20 25 30 35
No. at risk 1st TKI 14 4 3 2 1 0 0 0 2nd TKI 10 6 2 2 1 1 0 0
100
90
80
70
60
50
40
30
20
10
0 P
FS
(%
)
Months
0 5 10 15 20 25 30 35
No. at risk 1st TKI 9 6 4 2 1 0 0 0 2nd TKI 8 5 5 2 1 1 1 0
100
90
80
70
60
50
40
30
20
10
0
PF
S (
%)
Months
0 5 10 15 20 25 30 35
No. Median (mo) 95% CI 1st TKI 30 3.6 0.1-7.1 2nd TKI 21 11.0 0-22.8
Log rank P=0.24 Log rank P=0.07
No. Median (mo) 95% CI 1st TKI 9 8.2 2.1-14.3 2nd TKI 8 11.0 0-26.1
No. Median (mo) 95% CI 1st TKI 14 2.6 2.1-3.1 2nd TKI 10 18.3 0-39.2
No. Median (mo) 95% CI 1st TKI 21 2.8 2.1-3.4 2nd TKI 13 18.3 3.2-33.4
Log rank P=0.12
41
First-line Clinical Data: Prospective Efficacy Assessments
in the LUX-Lung Programme • Of 600 patients given afatinib in LUX-Lung 2/3/6, 75 (12%) patients had uncommon EGFR mutations1
• The LUX-Lung programme provides the largest series of prospective efficacy data in uncommon
mutations1-4
1. Yang et al. Lancet Oncol. 2015;16:830; 2. Passaro et al. J Thorac Dis. 2013;5:383; 3. Katakami et al. J Clin Oncol. 2013;31:3335; 4. Wu et al. Lancet Oncol. 2014;15:213;
5. Yang et al. Lancet Oncol. 2012;13:539; 6. Sequist et el. J Clin Oncol. 2013;31:3327.
aEGFR mutations detected by TheraScreen EGFR29 test. Common: 19 deletions in exon 19 and L858R in exon 21; Uncommon: 3 insertions in exon 20, L861Q, T790M, G719S, G719A and G719C, and S768I.
LUX-Lung 2
Phase 2 (N=129)5
Afatinib
First- and second-line (after chemotherapy)
Direct sequ. (central)
Del19=52 L858R=54
N=23 N=23
LUX-Lung 3
Phase 3 (N=345)6
Afatinib vs Cis/Pem
First-line
EGFR29a (central)
Del19=170 L858R=138
N=37 N=26
LUX-Lung 6
Phase 3 (N=364)4
Afatinib vs Cis/Gem
First-line
EGFR29a (central)
Del19=186 L858R=138
N=40 N=26
Common mutations
Uncommon mutations; treated with afatinib4
Mutation test
Line of treatment
Treatment
42
LUX-Lung 2, 3, and 6: Tumour Shrinkage by Independent
Review (n=67a)
• 3 patients in group 1 achieved complete response
– 1 each with G719X, K739_1744dup6, and L858R+Q709G/V
Yang et al. Lancet Oncol. 2015;16:830.
a8 patients w ere not included because of insuff icient data. bT790M alone.
-100
-80
-60
-40
-20
0
20
40
60
80
100
120
b
b
b
Ma
xim
um
ch
an
ge
fro
m
ba
se
lin
e (
%)
Group 2 (n=14): de novo T790M mutations T790M alone, T790M+Del19, T790M+L858R, T790M+G719X, T790M+L858R+G719X
Group 1 (n=33): point mutations or duplications in exons 18-21 L861Q, G719X, G719X+S768I, G719X+L861Q, E709G or V+L858R, S768I+L858R,
S768I, L861P, P848L, R776H+L858R, L861Q+Del19, K739_1744dup6
Group 3 (n=20): exon 20 insertions
43
LUX-Lung 2, 3, and 6: Response Rate, PFS, and OS by
Independent Review
Yang et al. Lancet Oncol. 2015;16:830.
T790M
(n=14)
Exon 20 ins
(n=23)
Mut/Dup
Exon 18-21
(n=38)
G719X
(n=18)
L861Q
(n=16)
S768I
(n=8)
Response rate
(%) 14.3 8.7 71.1 77.8 56.3 100.0
PFS (mo) 2.9 2.7 10.7 13.8 8.2 14.7
OS (mo) 14.9 9.2 19.4 26.9 17.1 NE
44
Summary
• Afatinib has shown preclinical and clinical activity in TKI-naive and TKI-pretreated
patients with NSCLC harbouring uncommon EGFR mutations
• Activity of afatinib against uncommon EGFR mutations in patients with LMD was also
reported
• Afatinib was especially active in NSCLC tumours harbouring point mutations or
duplications in exons 18-21 (eg, G719X, S768I, L861Q K739_1744dup6, and
L858R+Q709G/V)
• Anecdotal data from erlotinib/gefitinib trials show variable and mainly limited
responses to these EGFR TKIs in patients with NSCLC harbouring uncommon
mutations
• These data could help inform clinical decisions for patients with NSCLC harbouring
uncommon EGFR mutations
45
Yokohama, when sunny, and in later fall…
We are
HERE Just 3 train stops,
or 30 min. walk!
Ocean liner Hikawa maru, Yamashita Park
For more information about other BI events and collaborations, please visit www.inOncology.com
Considerations for Choosing TKIs for Squamous NSCLC in the
Era of Immunotherapy: Which Patients Could Benefit?
2017 WCLC- PACIFICO Yokohama Convention Center
Barbara Melosky
University of British Columbia,
British Columbia Cancer Agency
BI Symposium
48
Faculty Disclosure
• Honoraria: Boehringer Ingelheim, Merck, Eli Lilly, Bristol-Myers Squibb,
Novartis, Pfizer, AstraZeneca
49
Squamous Cell Carcinoma (SqCC) of the Lung
• Squamous histology represents approximately 20–40% of
NSCLC1,2
• SqCC of the lung remains a disease with high unmet need
• SqCC of the lung is associated with poor prognosis3
• Targetable oncogenic alterations are few
• Additional therapeutic options are needed
1. Ho C et al. Curr Oncol. 2015;22:e16 4–e170; 2. Bryant A and Cerfolio RJ. Chest. 2007;132:185–92; 3. Cetin K et al. Clin Epidemiol. 2011;3:139–48.
OS = overall survival; NSCLC = non-small cell lung cancer.
50
Current Treatment Recommendations for Metastatic
SqCC of the Lung
1. Novello S et al. Ann Oncol. 2016;27(suppl 5):v1–v27.
*ESMO guidelines do not recommend maintenance therapy in the treatment of squamous cell carcinoma NSCLC. 1 BSC = Best Standard of Care; EGFR = epidermal growth f actor receptor;
MCBS = Magnitude of Clinical Benef it Scale; NSCLC = non-small cell lung cancer; PD-L = programmed death-ligand; PS = Perf ormance Status; SqCC = squamous cell carcinoma.
Nivolumab (I, A; MCBS 5)
Pembrolizumab if PD-L1>1%
(I, A; MCBS 3 if PD-L1 >1%; MSBC 5 if PD-L1
>50%)
Docetaxel (I, B)
Ramucirumab – docetaxel (I, B; MCBS 2)
Erlotinib (II, C)
Afatinib (I, C; MCBS 1)
PS 3–4
Disease progression
Never or former light
smoker (<15 pack/year)
I) Age
II) PS
<70 years and PS 2
or
>70 years and PS 0–2
PS 0–2
Molecular test
(ALK/EGFR)
Molecular test
positive
Molecular test
negative
Targeted therapy
<70 years and PS 0-1
PS 3–4
BSC (II, B)
4–6 cycles: Cisplatin – gemcitabine (I, A)
Cisplatin – docetaxel (I, A)
Cisplatin – vinorelbine (I, A) Carboplatin – paclitaxel (I, A)
Carboplatin – nab-paclitaxel (I, B) Cisplatin – gemcitabine – necitumumab
(if EGFR expression by IHC)
(I, B; MCBS 1)
4–6 cycles: Carboplatin-based doublets (II, B)
Single-agent chemotherapy
(gemcitabine, vinorelbine or docetaxel) (I,A)
BSC
Stage IV SqCC
51
Overview of Recent Key Phase III ≥ Second-line
Treatment Studies in Patients With SqCC of the Lung
1. Garon E et al. Lancet. 2014;384:665–73; 2. Brahmer J et al. N Engl J Med. 2015;373:123–35; 3. Herbst R et al. Lancet. 2016;387:1540–50; 4. Soria JC et al.
Lancet Oncol. 2015;16:897–907; 5. Rittmeyer A et al. Lancet. 2017;389:255–65.
Trial Treatment Median PFS (mo) HR for PFS Median OS (mo) HR for OS ORR (%)
REVEL1
Ramucirumab + doce vs doce (n=1253) Squamous (n=328)
4.5 vs 3.0 4.2 vs 2.7
0.76* 0.76*
10.5 vs 9.1 9.5 vs 8.2
0.86* 0.88
22.9 vs 13.6* 26.8 vs 10.5*
CheckMate-0172 Nivolumab vs doce All squamous (n=272)
3.5 vs 2.8
0.62*
9.2 vs 6.0
0.59*
20.0 vs 9.0*
KEYNOTE-0103
Pembrolizumab vs doce PD-L1 PS ≥50% (n=442) Squamous (n=222)
2 mg: 5.0 vs 4.1 10 mg: 5.2 vs 4.1 NR for squamous
2 mg: 0.59* 10 mg: 0.59*
0.86
14.9 vs 8.2 17.3 vs 8.2
NR for squamous
0.54* 0.50* 0.74
30.0 vs 8.0* 29.0 vs 8.0*
NR for squamous
LUX-Lung 84 Afatinib vs erlotinib (n=795) All squamous
2.6 vs 1.9
0.81*
7.9 vs 6.8
0.81*
6.0 vs 2.8*
OAK5 Atezolizumab vs doce (n=850) Squamous (n=222)
2.8 vs 4.0 NR for squamous
0.95 NR for squamous
13.8 vs 9.6 8.9 vs 7.7
0.73* 0.73*
14 vs 13 NR for squamous
All agents listed are FDA and EMEA approved for the treatment of SqCC of the lung.
*P<0.05.
doce = docetaxel; EMEA = European Medicines Agency; FDA = US Food and Drug Administration; HR = hazard ratio; mo = months; NR = not reported; ORR = objective
response rate; OS = overall survival; PD-L1 = programmed death-ligand 1; PFS = progression-free survival; PS = proportion score; SqCC = squamous cell carcinoma.
52
ESMO Guidelines: Second-line Recommendations
Nivolumab (I, A; MCBS 5)
Pembrolizumab if PD-L1>1%
(I, A; MCBS 3 if PD-L1 >1%; MSBC 5 if PD-L1 >50%
Docetaxel (I, B)
Ramucirumab – docetaxel (I, B; MCBS 2)
Erlotinib (II, C)
Afatinib (I, C; MCBS 1)
;
MCBS = Magnitude of Clinical Benef it Scale; PD-L = programmed death-ligand.
1. Novello S et al. Ann Oncol. 2016;27(suppl 5):v1–v27.
53
SqCC of the Lung: Genetically Complex Malignancy • High burden of somatic mutations/genomic alterations1
• Overexpression/derangements of EGFR,2,3 HER2,4,5 HER4,6 and/or dysregulation of their downstream pathways
implicated in the pathogenesis of SqCC of the lung
1. Law rence et al. Nature. 2013;499:214; 2. López-Malpartida et al. Lung Cancer. 2009;65:23; 3. Hirsch et al. J Clin Oncol. 2003;21:3796; 4. Heinmoller et al. Clin Cancer Res.
2003;9:5238; 5. Ugocsai et al. Anticancer Res. 2005;25:306; 6. Cancer Genome Atlas Research Netw ork. Nature. 2012;489:519.
Pilo
cytic
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denocarc
inom
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-cell
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bla
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ALL
54
ErbB Pathway is Frequently Dysregulated in SqCC
of the Lung
1. Hirsch FR et al. J Clin Oncol. 2003;21:3798–807; 2. Lopez-Malpartida AV et al. Lung Cancer. 2009;65:25–33; 3. Lee HJ et al. Lung Cancer. 2010;68:375–82; 4. Gately K et al. Clin Lung Cancer. 2014;15:58–66; 5. Dacic S et al. Am J Clin Pathol. 2006;125:860–5; 6. Ji H et al. Proc Natl Acad Sci U S A. 2006;103:7817–22; 7. Dearden S et al. Ann Oncol. 2013;24:2371–6; 8. Jaiswal BS et al. Cancer Cell. 2013;23:603–17; 9. Gorgoulis V et al. Pathol Res Pract.
1995;191:973–81; 10. Kan Z et al. Nature. 2010;466:869–73; 11. Shepherd FA et al. N Engl J Med. 2005;352:123–32; 12. Clark GM et al. Clin Lung Cancer. 2006;7:389–94; 13. Leon et al. ESMO 2008. Abstract 1277 (poster);
14. Pirker R et al. Lancet. 2009;373:1525–31; 15. Pirker R et al. Lancet Oncol. 2012;13:33–42; 16. Thatcher N et al. ASCO 2014. Abstract 8008; 17. Li T et al. J Clin Oncol. 2013;31:1039–49.
Amp = amplif ication; EGFR = epidermal grow th factor receptor; FGFR = fibroblast grow th factor receptor; SqCC = squamous cell carcinoma.
ErbB Receptor Frequency
(%)
EGFR overexpression2–5 26–86
EGFR amplification2,5 15–27
EGFRvIII mutation6 5
EGFR kinase domain mutation7 <5%
ERBB2 mutation/amplification2 5
ERBB3 mutation8 1
ERBB3 overexpression9 10
ERBB410 8
Frequency of known genetic drivers in SqCC17
– EGFR overexpression, gene
amplification and aberrations of other
ErbB receptors have all been implicated
in the pathobiology of SqCC1,2
– These findings likely account for the
benefits these patients derive from
erlotinib11–13 and other EGFR-directed
therapies in different treatment
settings,14–16 despite the low frequency
of EGFR-activating mutations17
EGFRvIII
PI3KCA
EGFR
DDR2
FGFR1 Amp
Unknow n
~5%
55
Afatinib is the First Irreversible ErbB Family Blocker
1. Li et al. Oncogene. 2008;27:4702; 2. Solca et al. J Pharmacol Exp Ther. 2012;343:342.
• Afatinib covalently binds and
irreversibly blocks EGFR, HER2,
and ErbB4
• Targeting the whole ErbB Family enhances the effect on important
signaling pathways
56
LUX-Lung 8: Study Design
1. Soria JC et al. Lancet Oncol. 2015;16:897–907.
• Advanced SqCC NSCLC (Stage IIIB/IV)
• PD after ≥4 cycles of a first-line
platinum doublet
• ECOG PS 0 or 1
• No prior anti-EGFR therapy
• No active brain metastases
Afatinib (n=398)
40 mg qd
Erlotinib (n=397)
150 mg qd
Treatment
until disease
progression
or
unacceptable
AEs
Randomisation
1:1
(N=795)
• Stratification: East Asian vs non-East Asian
• Tumour tissue collected for correlative science
• Radiographic tumour assessment at baseline; Weeks 8, 12, 16; every 8 weeks
thereafter
• Primary endpoint: PFS; key secondary endpoint: OS
AE = adverse event; EGFR = epidermal grow th factor receptor; ECOG PS = Eastern Cooperative Oncology Group performance status; NSCLC = non-small cell lung cancer;
OS = overall survival; PD = disease progression; PFS = progression-free survival; qd = once daily; SqCC = squamous cell carcinoma.
57
1.0
LUX-Lung 8: Significant Improvement in PFS and OS
With Afatinib Compared With Erlotinib
1. Soria JC et al. Lancet Oncol. 2015;16:897–907.
397 99 34 17 10 2 0 1 1 1 Erlotinib
398 139 50 30 14 10 5 2 2 0
397 99 34 17 10 2 1 1 1 0
398 316 249 170 124 82 47 28 10 4 0
397 305 210 150 94 54 30 11 4 2 0
Afatinib
40 mg QD
(n=398)
Erlotinib
150 mg QD
(n=397)
Patients progressed or died, n (%) 299 (75.1) 306 (77.1)
Median PFS (months) 2.6 1.9
HR 0.81; 95% CI: 0.69–0.96;
P=0.0103
Afatinib
40 mg QD
(n=398)
Erlotinib
150 mg QD
(n=397)
Patients died, n (%) 307 (77.1) 325 (81.9)
Median OS (months) 7.9 6.8
HR 0.81; 95% CI: 0.69–0.95;
P=0.0077
Primary analysis of OS (key secondary endpoint) (n=795)
Pro
ba
bil
ity o
f P
FS
Updated PFS analysis by Independent Review (n=795)
3 6 9 12 15 18 21 24
0.2
0.4
0.6
0.8
0 0 27 3 6 9 12 15 30 18 21 24 27
0.2
0.4
0.6
0.8
1.0
0 0
36.4%
28.2% 22.0%
14.4%
Time (months) Time (months)
Pro
ba
bil
ity o
f O
S
Afatinib
Erlotinib
Afatinib
Erlotinib
No. at risk No. at risk
CI = confidence interval; HR = hazard ratio; OS = overall survival; PFS = progression-free survival; QD = once daily.
58
Post-hoc Analysis of LUX-Lung 8 Patients Deriving
Long-term Benefit1
1. Yang J et al. ELCC 2017. Poster #102P.
Post-hoc analysis identified 21 patients who received ≥12 months of afatinib
treatment
– Median treatment duration was 17.6 months (range: 12.3–27.6 months)
59
Post-hoc Analysis of LUX-Lung 8 Patients Deriving
Long-term Benefit1
1. Yang J et al. ELCC 2017. Poster #102P.
OS: Primary Analysis
(ITT population)
1.0
0.8
0.6
0.4
0.2
0
0 3 6 9 12 15 18 21 24 27 30
Time (months)
Es
tim
ate
d O
S p
rob
ab
ilit
y
36.4%
22.0%
28.2%
14.4%
Afatinib (n=398)
Erlotinib (n=397) • Median OS was 21.1 months
(range: 12.9–31.6 months)
• Median PFS was 16.6 months
(range: 2.8–25.8 months)
Afatinib OS, 7.9 mo
OS and PFS in Patients
Deriving Long-term Benefit
60
Treatment Response* and OS in Patients Deriving
Long-term Benefit
Yang J et al. ELCC 2017. Poster #102P.
*Stable disease unless noted otherw ise (patient 2 w as classified as non-evaluable); †Patients w ere ordered and numbered by treatment duration, w ith patient 1 being on
treatment longest; ‡First observed response at time of tumour measurement; §Last observed response at time of tumour measurement; ¶Treatment ongoing until death;
‖Received ≥1 line of chemotherapy after afatinib; CR = complete response; PR = partial response.
• Median OS was 21.1 months (range: 12.9–31.6 months)
• Median PFS (independent central review) was 16.6 months (range: 2.8–25.8 months)
61
Genomic Aberrations in Patients Deriving Long-term
Benefit
• ErbB family mutations were more frequent in LTRs than in the overall afatinib-treated
population
Yang J et al. ELCC 2017. Poster #102P.
*Next-generation sequencing w as undertaken in 10/21 LTRs and 132/398 afatinib-treated patients overall; WT = w ild-type.
LTRs (n=10*)
ErbB3, 0% ErbB4,
10.0%
ErbB WT, 50.0%
ErbB2, 20.0%
EGFR, 20.0%
All afatinib-treated patients (n=132*)
ErbB4, 2.3%
ErbB WT, 81.1%
ErbB2, 6.8%
EGFR, 6.8%
ErbB3, 4.6%
62
Experience With Afatinib for SqCC of the Lung:
Case Report From LUX-Lung 8
Baseline characteristics
• 59-year-old white male
• ECOG PS: 1
• Stage IV
• Primary site: left upper lobe
• Number of metastases: 2; no brain metastases
• Smoking status: ex smoker (41 pack-years)
Treatments
• First-line: carboplatin/paclitaxel (Aug 2012 to Oct 2012; best response: CR); no maintenance therapy
• Second-line: afatinib within LUX-Lung 8
Case study.
BMI = body mass index; COPD = chronic obstructive pulmonary disease; CR = complete response; DC = discontinued; ECOG PS = Eas tern Cooperative Oncology Group
performance status; OS = overall survival; PD = disease progression; PFS = progression-free survival; SqCC = squamous cell carcinoma.
63
Experience With Afatinib for SqCC of the Lung:
Case Report From LUX-Lung 8
Outcomes with second-line afatinib
• Treatment duration: 19.6 months (Mar 2013 to Nov 2014)
– Afatinib dosage: 40 mg for 28 days; 50 mg for 18.7 months
• PFS: 17.1 months • OS: 23.1 months
Biomarker analysis
• Mutation: HER2 E395K
Case study.
BM = bone metastasis; BMI = body mass index; COPD = chronic obstructive pulmonary disease; CR = complete response; DC = discontinued; ECOG PS = Eastern
Cooperative Oncology Group performance status; OS = overall survival; PD = disease progression; PFS = progression-free survival; SqCC = squamous cell carcinoma.
64
See You at the Poster!
• P3.01 – Advanced NSCLC (ID 621)
09:30 am – 04:00 pm | 10/18/2017 | Location: Exhibit Hall (Hall B + C)
Type: Poster Session with Presenters Present | Track: Advanced NSCLC
– P3.01-043 – Impact of ErbB Mutations on Clinical Outcomes in Afatinib- or
Erlotinib-Treated Patients with SCC of the Lung
Presenting Author: Glenwood Goss | Authors(s): Enriqueta Felip, M. Coco, Shun Lu, K. Syrigos, K.H. Lee, E. Göker, V. Georgoulias, W. Li, S. Guclu, D. Isla, Y. Joo Min, A. Morabito, A. Ardizzoni, Shirish M. Gadgeel, N. Gibson, N. Krämer, F. Solca,
A. Cseh, E. Ehmrooth, J. Soria
65
Summary and Conclusions
• LUX-Lung 81
Afatinib significantly improved PFS vs erlotinib: 2.6 vs 1.9 months
(HR 0.81; P=0.0427)
Afatinib significantly improved OS vs erlotinib: 7.9 vs 6.8 months
(HR 0.81, P=0.0077)
– Survival rates at 12 and 18 months favored afatinib
12 months (afatinib vs erlotinib): 36% vs 28% (P=0.016)
18 months: 22% vs 14% (P=0.013)
– In patients on afatinib for ≥ 12 months, a median survival benefit of nearly 2 years
was seen
ErbB family mutations were more frequent in this group3
1. Soria JC et al. Lancet Oncol. 2015;16:897–907; 2. Goss G et al. WCLC 2016; Presentation OA23.03; 3. Yang J et al. ELCC 2017. Poster #102P.
HR = hazard ratio; OS = overall survival; PFS = progression-free survival; SqCC = squamous cell carcinoma.
66
Summary and Conclusions
In treatment of SqCC, afatinib should be considered:
As a treatment option in patients who have failed previous
treatment with chemotherapy and immunotherapy
In the second-line setting in patients who are not eligible for
immune checkpoint inhibitors
1. Soria JC et al. Lancet Oncol. 2015;16:897–907; 2. Goss G et al. WCLC 2016; Presentation OA23.03; 3. Yang J et al. ELCC 2017. Poster #102P.
HR = hazard ratio; OS = overall survival; PFS = progression-free survival; SqCC = squamous cell carcinoma.
For more information about other BI events and collaborations, please visit www.inOncology.com
Panel Discussion Carrying the Data into the Clinic:
TKI Sequencing Decisions for EGFR Mutation-Positive NSCLC Patients
2017 WCLC- PACIFICO Yokohama Convention Center
All Faculty
Moderator: T. Mitsudomi
BI Symposium
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What next?
Visit our medical education site www.inOncology.com
Visit www.inoncology.com to download materials, watch our webcast
and find more answers to your questions.