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Title slide
OS across 7 trials
1
Overview slide
3 months OS
13.6 months PFS
> 12 month OS
Symptom control
Summary slide
QoL
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Title slide
OS across 7 trials
Overview slide
3 months OS
Subsequent therapy
2
PFS comparison
13.6 months PFS
Symptom control
> 12 month OS
Summary slide
OS Forest Plot Del 19
OS Forest Plot L858R
QoL
PFS Forest Plot L858R
GIOTRIF® - First targeted
therapy to show significant
first-line OS benefit in
EGFR M+ NSCLC*1
3
GIOTRIF® (afatinib) as monotherapy is indicated for the treatment of Epidermal Growth Factor Receptor (EGFR) TKI- naïve adult
patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutation(s).
* Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs
chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin).
EGFR M+=epidermal growth factor receptor mutation positive; NSCLC=non-small cell lung cancer; OS=overall survival.
1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
GIOTRIF® – First approved irreversible ErbB Family Blocker1
13.6 months PFS
(del19/L858R)*2
Significantly
better QoL†4
4
Significant
Overall Survival
benefit**3
Clinically meaningful
Symptom
Improvement†4
* vs pemetrexed/cisplatin in prespecified subgroup of patients with common mutations (del19/L858R); ** Secondary endpoint,
primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung
3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). † vs pemetrexed/cisplatin.
PFS=progression-free survival; QoL=quality of life.
1.Solca F et al. J Pharmacol Exp Ther. 2012;343(2):342-350.
2.Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
3.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
4.Yang JC et al. J Clin Oncol. 2013;31(27):3342-3350.
GIOTRIF® – First approved irreversible ErbB Family Blocker1
13.6 months PFS
vs. pemetrexed/cisplatin
(del19/L858R)*2
Significantly better QoL
vs. pemetrexed/cisplatin†4
Significant Overall
Survival benefit
vs. pemetrexed/cisplatin or
gemcitabine/cisplatin **3
Clinically meaningful
Symptom Improvement
vs. pemetrexed/cisplatin†4
5
* vs pemetrexed/cisplatin in prespecified subgroup of patients with common mutations (del19/L858R); ** Secondary endpoint,
primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung
3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). † vs pemetrexed/cisplatin.
PFS=progression-free survival; QoL=quality of life.
1.Solca F et al. J Pharmacol Exp Ther. 2012;343(2):342-350.
2.Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
3.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
4.Yang JC et al. J Clin Oncol. 2013;31(27):3342-3350.
GIOTRIF® – Superior first-line PFS vs pemetrexed/cispatin in
common mutations (del19/L858R)1
LUX-Lung 3 prespecified subgroup analysis
Del9/L858R mutations
1.0
GIOTRIF® (n=204)
Pemetrexed/cisplatin (n=104)
13.6
months
PFS rate (%)
0.8
Hazard ratio 0.47
(95% CI, 0.34-0.65)
P<0.001
0.6
0.4
6.9
months
0.2
0.0
0
3
6
9
12
15
18
21
24
Time (months)
• ~90% of patients in LUX-Lung 3 had common mutations (del19/L858R)
6
PFS=progression-free survival.
1.Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
27
GIOTRIF® – Longer PFS than reversible TKIs when indirectly
compared
PFS in first-line phase III registration trials in NSCLC
14
13.6*†
Median PFS (months)
12
9.5‡
9.7*
10
8
6.9*†
6.3‡
6
5.2*
4
2
0
GIOTRIF®
Cisplatin +
Pemetrexed
LUX-Lung 31
7
Erlotinib
Cisplatin/
carboplatin +
gemcitabine/
docetaxel
EURTAC2
Gefitinib
Carboplatin +
Paclitaxel
IPASS3
The data presented above come from separate studies with different designs and therefore results cannot be directly compared.
* Common EGFR mutations (Del19/L858R); † Prespecified subgroup analysis (89% of patients); ‡ Common and uncommon
muatations; PFS=progression-free survival; TKI=tyrosine kinase inhibitor.
1.Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
2.Rosell R et al. Lancet Oncol. 2012;13(3):239-46.
3.Mok TS et al. New Engl J Med 2009;361:947-957.
GIOTRIF® – Delayed time to deterioration of clinically relevant
symptoms1
LUX-Lung 3: TTD of symptoms (EORTC QoL QLQ-C30 and QLQ LC-13)
Median not
reached
8.0
Cough
p=0.007
>97%
2.9
Dyspnoea
10.3 months
p=0.015
3.1
Pain
4.2 months
questionnaire
completion
GIOTRIF® (n=230)
p=0.19
0
2
4
6
8
10
12
Median TTD (months)
8
TTD=time to deterioration.
EORTC=European Organisation for Research and Treatment of Cancer.
1.Yang JC et al. J Clin Oncol. 2013;31(27):3342-3350.
14
16
Cis/Pem (n=115)
GIOTRIF® –
Significantly improved QoL vs pemetrexed/cisplatin1
LUX-Lung 3: EORTC QLQ-C30 questionnaire scores longitudinal analysis
Favours GIOTRIF®
Favours pem/cis
Significant difference
favouring GIOTRIF®
Global health status/QoL
Physical functioning
Role functioning
Cognitive functioning
Emotional functioning
Social functioning
>97%
-10
-5
0
Differences in mean scores (95% confidence intervals)
9
Qo=quality of life.
EORTC=European Organisation for Research and Treatment of Cancer.
1. Yang JC et al. J Clin Oncol. 2013;31(27):3342-3350.
5
questionnaire
completion
No first-line OS benefit demonstrated with reversible EGFR TKIs
First-line phase III trials with reversible EGFR TKIs
Reversible
EGFR TKI
Registration trial
Hazard ratio
Overall survival
p value
EURTAC1
Erlotinib
Yes
0.93
NS
IPASS2
Gefitinib
Yes
1.0
NS
ENSURE3
Erlotinib
No
N/A
NS
OPTIMAL4
Erlotinib
No
1.04
NS
NEJ0025
Gefitinib
No
0.89
NS
WJTOG34056
Gefitinib
No
1.25
NS
FIRST-SIGNAL7
Gefitinib
No
1.04
NS
Trial
10
N/A=not applicable; NS=not significant; OS=overall survival; TKI=tyrosine kinase inhibitor.
1.TARCEVA® (erlotinib) prescribing information, 2013.
2.Fukuoka et al. J Clin Oncol. 2011;29:2866-74.
3.Wu et al. J Thorac Oncol. 2013;8:suppl 2 (P1.11-021)
4.Zhou et al. J Clin Oncol 30, 2012 (suppl; abstr 7520).
5.Inoue et al. Ann Oncol. 2013;24:54-59.
6.Yoshioka H, et al. J Clin Oncol 32:5s, 2014 (suppl; abstr 8117).
7.Han et al. J Clin Oncol. 2012;30:1122-8.
GIOTRIF® – Significantly increased first-line OS vs
chemotherapy*1
Post-hoc combined analysis (LUX-Lung 3 & 6)
Del19/L858R mutations
Estimated OS probability
1.0
GIOTRIF® (n=419)
Chemotherapy (n=212)
27.3
months
0.8
Hazard ratio 0.81
(95% CI, 0.66-0.99)
P=0.0374
0.6
+3
months
0.4
median OS
24.3
months
0.2
0.0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
45
48
51
Time of overall survival (months)
• The proportion of patients who received subsequent therapies was balanced in both arms
• OS in ITT population (N=345) was 28.16 and 28.22 months for GIOTRIF® vs
pemetrexed/cisplatin, respectively (HR 0.88, 95% CI, 0.66-1.17;
P=0.3850)
11
* Secondary endpoint, primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (Del19/L858R) vs
chemotherapy (LUX-lung 3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). ITT=intent to treat; OS=overall survival.
1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
GIOTRIF® – balanced subsequent therapy validates OS
outcome1
Subsequent therapy in LUX-Lung 3 and 6
(% patients) with subsequent therapy
Trial
GIOTRIF®
Pem/cis or gem/cis
LUX-Lung 3
71% chemo
75% EGFR TKI
LUX-Lung 6
59% chemo
56% EGFR TKI
• The proportion of patients who received subsequent therapies was balanced
in both arms
12
TKI = tyrosine kinase inhibitor.
1. Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
GIOTRIF® – Pronounced OS benefit in del19 (exon 19) patients1
LUX-Lung 3 overall survival
Del19 mutations
Estimated OS probability
1.0
GIOTRIF® (n=112)
Pemetrexed/cisplatin (n=57)
33.3
months
0.8
Hazard ratio 0.54
(95% CI, 0.36-0.79)
P=0.0015
0.6
0.4
>12
months
increase
21.1
months
0.2
median OS
0.0
0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
45
48
51
Time of overall survival (months)
• Over 1 year extended survival with GIOTRIF® vs pem/cis in del19 (exon 19) patients
(P=0.0015)
• Over 1 year extended survival also demonstrated in LUX-Lung 6
13
OS=overall survival.
1. Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
GIOTRIF® – First targeted therapy to offer del19 (exon 19)
patients a significant OS benefit1-6
OS in registration trials in del19 (exon 19) patients
Favours targeted therapy
Favours chemotherapy
HR (95% CI)
LUX-Lung 31
0.54 (0.36 – 0.79)
LUX-Lung 61
0.64 (0.44 – 0.94)
Gefitinib
IPASS2,3
0.79 (0.54 – 1.15)
Erlotinib
EURTAC4,5
0.94 (0.57 – 1.54)
GIOTRIF®
1/4
1
4
• ~50% of patients in LUX-Lung 3 and 6 had del19 mutations
14
OS=overall survival; HR=hazard ratio.
1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
2.Mok et al. N Engl J Med. 2009;361:947-57.
3.Yang et al. Eur J of Cancer. 2011 (suppl1;S633).
4.Rosell et al. Lancet Oncol. 2012;13:239-46.
5.TARCEVA® (erlotinib) prescribing information
16
No OS benefit yet demonstrated by targeted therapies in
L858R (exon 21) patients1-6
OS in registration trials in L858R (exon 21) patients
Favours targeted therapy
Favours chemotherapy
HR (95% CI)
LUX-Lung 31
1.30 (0.80 – 2.11)
LUX-Lung 61
1.22 (0.81 – 1.83)
Gefitinib
IPASS2-4
1.44 (0.90 – 2.30)
Erlotinib
EURTAC5,6
0.99 (0.56 – 1.76)
GIOTRIF®
1/4
1
4
• ~40% of patients in LUX-Lung 3 and 6 had L858R mutations
15
OS=overall survival; HR=hazard ratio.
1.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
2.Mok et al. N Engl J Med. 2009;361:947-57.
3.Fukuoka et al. J Clin Oncol. 2011;29:2866-74.
4.Yang et al. Eur J of Cancer. 2011 (suppl1;S633).
5.Rosell et al. Lancet Oncol. 2012;13:239-46.
6.TARCEVA® (erlotinib) prescribing information
16
GIOTRIF® – Superior PFS vs chemotherapy in L858R (exon 21)
patients
PFS in registration trials in L858R (exon 21) patients
Favours targeted therapy
Favours chemotherapy
0.60 (0.39 – 0.93)
LUX-Lung 31
GIOTRIF®
HR (95% CI)
Investigator review
0.32 ( 0.19 – 0.52)
LUX-Lung 62
Independent review
Gefitinib
0.55 (0.35 – 0.87)
IPASS3,4
Investigator review
Erlotinib
0.55 ( 0.29 – 1.02)
EURTAC5
Investigator review
1/4
16
OS=overall survival, HR=hazard ratio.
1.Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
2.Wu YL et al. Lancet Oncol. 2014;15(2):213-22.
3.Mok et al. N Engl J Med. 2009;361:947-57.
4.Fukuoka et al. J Clin Oncol. 2011;29:2866-74.
5.Rosell et al. Lancet Oncol. 2012;13:239-46.
1
4
16
GIOTRIF® – Longer, better life for your patients*1,2
13.6 months PFS
(del19/L858R)*2
Significantly
better QoL†4
17
Significant
Overall Survival
benefit**3
Clinically meaningful
Symptom
Improvement†4
* vs pemetrexed/cisplatin in prespecified subgroup of patients with common mutations (del19/L858R); ** Secondary endpoint,
primary endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung
3 vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). † vs pemetrexed/cisplatin.
PFS=progression-free survival; QoL=quality of life.
1.Solca F et al. J Pharmacol Exp Ther. 2012;343(2):342-350.
2.Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
3.Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
4.Yang JC et al. J Clin Oncol. 2013;31(27):3342-3350.
Back-up
18
Majority of patients in LUX-Lung 3 had del19 (exon 19)
mutations
49%
Del19 (exon 19)
11%
uncommon
40%
L858R (exon 21)
• Del19 (exon 19) and L858R (exon 21) mutations represent approximately 90% of EGFR
mutations in NSCLC
— Del19 mutations consist of in-frame deletions of amino acids 747-750
— L858R mutations are exon 21 point mutations
19
1. Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
GIOTRIF® - superior first-line PFS vs pemetrexed/cisplatin1
LUX-Lung 3 PFS by independent review
All EGFR mutations
1.0
GIOTRIF® (n=230)
Pemetrexed/cisplatin (n=115)
11.1
months
PFS rate (%)
0.8
Hazard ratio 0.58
(95% CI, 0.43-0.78)
P<0.001
0.6
0.4
6.9
months
0.2
0.0
0
3
6
9
12
15
18
21
24
27
Time (months)
At the time of primary analysis, a total of 45 (20%) patients treated with GIOTRIF® and 3 (3%) patients treated with chemotherapy were known to be alive
and progression-free and are censored in the above graph. The primary PFS analysis was conducted after a total of 221 PFS events; it included 152
patients (66.1%) in the GIOTRIF® arm
20
PFS=progression-free survival.
1. Sequist LV et al. J Clin Oncol. 2013;31(27):3327-3334.
GIOTRIF® - superior first-line PFS vs gemcitabine/cisplatin1
LUX-Lung 6 PFS by independent review
All EGFR mutations
1.0
GIOTRIF® (n=242)
Pemetrexed/cisplatin (n=122)
11.0
months
PFS rate (%)
0.8
Hazard ratio 0.28
(95% CI, 0.20-0.39)
P<0.0001
0.6
0.4
5.6
months
0.2
0.0
0
3
6
9
12
15
Time (months)
21
PFS=progression-free survival.
1.Wu YL et al. Lancet Oncol. 2014;15(2):213-22.
18
21
24
27
GIOTRIF® – Delayed time to deterioration of clinically relevant
symptoms1
LUX-Lung 3: TTD of symptoms (EORTC QoL QLQ-C30 and QLQ LC-13)
Cough: significantly delayed TTD
Dyspnoea: significantly delayed TTD
Pain: trend to longer TTD
GIOTRIF®
n=230
Pem/cis
n=5
GIOTRIF®
n=230
Pem/cis
n=115
GIOTRIF®
n=230
Pem/cis
n=115
Not
reached
8.0
10.3
2.9
4.2
3.1
Median TTD
(months)
Median TTD
(months)
0.60
Hazard ratio
22
95% CI, 0.41-0.87
P=0.007
Median TTD
(months)
0.68
Hazard ratio
TTD=time to deterioration.
EORTC=European Organisation for Research and Treatment of Cancer.
1. Yang JC et al. J Clin Oncol. 2013;31(27):3342-3350.
95% CI, 0.50-0.93
P=0.015
0.82
Hazard ratio
95% CI, 0.62-1.10
P=0.19
Prespecified LUX-Lung 3 analysis, del19:
Over 2.5 years OS with 1 year improvement over pem/cis1
Prespecified LUX-Lung 3 analysis
Del19 mutations
Estimated OS probability
1.0
GIOTRIF® (n=112)
Pemetrexed/cisplatin (n=57)
33.3
months
0.8
Hazard ratio 0.54
(95% CI, 0.36-0.79)
P=0.0015
0.6
0.4
21.1
months
0.2
0.0
0
3
6
9
12
15
18
21
24
27
30
33
Time of overall survival (months)
23
OS=overall survival.
Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
36
39
42
45
48
51
Prespecified LUX-Lung 3 analysis, L858R:
Over 2 years OS1
Estimated OS probability
Prespecified LUX-Lung 3 analysis
L858R mutations
1.0
GIOTRIF® (n=91)
Pemetrexed/cisplatin (n=47)
0.8
Hazard ratio 1.30*
(95% CI, 0.80-2.11)
40.3
months
P=0.2919
0.6
0.4
27.6
months
0.2
0.0
0
3
6
9
12
15
18
21
24
27
30
33
Time of overall survival (months)
*HR=1.02 (0.62, 1.69), when adjusted for baseline imbalances
24
OS=overall survival.
Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
36
39
42
45
48
51
Prespecified LUX-Lung 6 analysis, del19:
Over 2.5 years OS with 1 year improvement over pem/cis1
Prespecified LUX-Lung 6 analysis
Del19 mutations
Estimated OS probability
1.0
GIOTRIF® (n=124)
Pemetrexed/cisplatin (n=62)
31.4
months
0.8
Hazard ratio 0.64
(95% CI, 0.44-0.94)
P=0.0229
0.6
0.4
18.4
months
0.2
0.0
0
3
6
9
12
15
18
21
24
27
30
33
Time of overall survival (months)
25
OS=overall survival.
1. Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
36
39
42
45
Prespecified LUX-Lung 6 analysis, L858R:
Over 1.5 years OS1
Estimated OS probability
Prespecified LUX-Lung 6 analysis
L858R mutations
1.0
GIOTRIF® (n=92)
Pemetrexed/cisplatin (n=46)
0.8
Hazard ratio 1.22
24.3
months
(95% CI, 0.81-1.83)
P=0.3432
0.6
0.4
19.6
months
0.2
0.0
0
3
6
9
12
15
18
21
24
27
30
33
Time of overall survival (months)
26
OS=overall survival.
1. Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
36
39
42
45
How do these results impact current practice?
All EGFR mutations
Superior PFS*
Significant improvements in symptoms and QoL*
Del19 (exon 19)
Over 2.5 years OS with 1 year
improvement over chemotherapy**
GIOTRIF® approved for use in
these patients
NCCN recommended (cat 1)
GIOTRIF® should be
the standard of care
for del19 patients
27
L858R (exon 21)
GIOTRIF® Approved for use in
these patients
NCCN recommended (cat 1)
GIOTRIF® continues to be a
treatment option
for L858R patients
* vs chemotherapy (LUX-Lung 3 pemetrexed/cisplatin, LUX-Lung 6 gemcitabine/cisplatin) ** Secondary endpoint, primary
endpoint was PFS; combined post-hoc analysis of common EGFR mutations (del19/L858R) vs chemotherapy (LUX-lung 3
vs pemetrexed/cisplatin and LUX-Lung 6 vs gemcitabine/cisplatin). OS=overall survival; PFS=progression-free survival;
QoL=quality of life; NCCN=National Comprehensive Cancer Network
Yang JC et al. ASCO oral presentation and abstract. J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^).
National Comprehensive Cancer Network Guidelines Version 4.2014.