1. until tumour progression until tumour progression
LUX Lung 7 Clinical Trial
LUX-Lung 7 is a randomised, open-label, phase IIb trial of afatinib versus gefitinib as a first-line treatment of patients with EGFR M+ advanced adenocarcinoma of the lung. 
afatinib
40 mg oral once daily
until tumour progression
Adenocarcinoma of the lung
Stage IIIb/IV
EGFR mutation (Del19 and/or L858R) in the tumour tissue
No prior treatment for advanced/metastatic disease
ECOG PS 0-1
1:1 randomisation
N=319
gefitinib
250 mg once daily
until tumour progression
Median follow-up: 27.4 months

2. Secondary endpoints included
LUX Lung 7 Study Endpoints
Primary endpoints
Progression-free survival (PFS) by independent review
Time to treatment failure (TTF): the time from randomisation to discontinuation for any reason, allowing continuation of treatment if physicians consider patients to be receiving clinical benefit
Overall survival (OS)
Secondary endpoints included
Objective response rate (ORR)
Time to and duration of response
Duration of disease control
Tumour shrinkage
Health related quality of life (HRQoL), as reported by EQ-5D patient questionnaires

3. LUX Lung 7: 64 sites in 14 countries
Recruitment: Dec 2011-Aug 2013
Canada 31
China 48
Hong Kong 6
Taiwan 22
Korea 56
Singapore 27
Germany 14
Spain 25
France 34
Norway 3
Sweden UK 7
Ireland 9
Australia 19

4. Patient demographics and characteristics were well balanced
between the 2 treatment arms
Afatinib
160, N (%)
Gefitinib
159, N (%)
Total
319, N (%)
Age, median yrs (min-max)
63 (30-86)
63 (32-89)
63 (30-89)
Gender
Female
91 (56.9)
106 (66.7)
197(61.8)
Male
69 (43.1)
53 (33.3)
122 (38.2)
Race
Asian
94 (58.8)
88 (55.3)
182 (57.1)
Non-Asian*
66 (41.2)
71 (44.7)
137 (42.9)
Brain mets
26 (16.3)
25 (15.7)
51 (16.0)
Never smoker
106 (66.3)
212 (66.5)
Baseline ECOG
51 (31.9)
47 (29.6)
98 (30.7) 1
109 (68.1)
112 (70.4)
221 (69.3)
NSCLC stage
IIIB
8 (5.0)
3 (1.9)
11 (3.5) IV
152 (95.0)
156 ( 98.1)
308 (96.6)
EGFR mutation
Del19#
93 (58.1)
93 (58.4)
186 (58.3)
L858R
67 (41.9)
66 (41.6)
133 (41.7)

5. LUX-LUNG 7
Efficacy

6. Progression-free survival by independent review (primary endpoint)
Afatinib demonstrated a 27% reduction in relative risk of death or progression compared to gefitinib
Progression-free survival by independent review (primary endpoint)
Estimated PFS probability
0.2
0.4
0.6
0.8
1.0
0.0
Median (months)
Afatinib® (n=160)
11.0
Gefitinib (n=159)
10.9
Hazard ratio 0.73
(95% CI, )
P=0.0165
27% vs 15%
18% vs 8% 3 6 9 12 15 18 21 24 27 30 33 36 39 42
Time of progression free survival (months)
Patients twice as likely to be alive and progression free at 2 years with afatinib vs gefitinib (18% vs 8%, respectively)
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

7. Afatinib – PFS benefit consistent across subgroups, including EGFR mutation type
Progression-free survival by independent review (primary endpoint) prespecified subgroups
Factors
Number of patients
Hazard ratio (95% Cl)
Total
319
0.732 (0.566, 0.947)
EGFR mutation
L858R
133
0.708 (0.475, 1.055)
Del19
186
0.764 (0.549, 1.063)
Brain métastasés
Absent
268
0.739 (0.560, 0.976)
Present 51
0.764(0.405, 1.439)
Baseline ECOG score 98
0.892 (0.542, 1.469) 1
221
0.705 (0.524, 0.948)
Gender
Maie
122
0.876 (0.585, 1.312)
Female
197
0.653 (0.469, 0.910)
Age group
<65 years
177
0.681 (0.479, 0.968)
>65 years
142
0.845 (0.585, 1.221)
Race
Non-Asian
137
0.717 (0.487, 1.056)
Asian
182
0.756 (0.539, 1.060)
Smoking hïstory
Never smoked
212
0.801 (0.584, 1.097)
<15 pack years + stopped >1 year before 40
1.094 (0.559, 2.140)
Other current or ex-smokers 67
0.477 (0.270, 0.845)
1/4 1 4 16
1/16
Favours afatinib
Favours gefitinib
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

8. Time to treatment failure (primary endpoint)
Patients remained on treatment significantly longer with afatinib than with gefitinib
Time to treatment failure (primary endpoint)
Estimated probability of being free of treatment failure
0.2
0.4
0.6
0.8
1.0
0.0
Median (months)
Afatinib® (n=160)
13.7
Gefitinib (n=159)
11.5
Hazard ratio 0.73
(95% CI, )
P=0.0073 3 6 9 12 15 18 21 24 27 30 33 36 39 42
Time to treatment failure (months)
27% significant reduction in relative risk of treatment failure vs gefitinib (P=0.0073)
Overall survival data not yet mature
TTF is the time from randomisation to discontinuation for any reason, allowing continuation of treatment if physicians consider patients to be receiving clinical benefit
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

9. Objective response by independent review (secondary endpoint)
Afatinib demonstrated significantly improved response rates vs gefitinib
Objective response by independent review (secondary endpoint)
P=0.0083
Afatinib
Gefitinib
Improved objective response and disease control rates vs gefitinib (ORR: 70% vs 56%, P=0.0083; DCR: 91.3% vs 87.4%)
Longer duration of response vs gefitinib (10.1 vs 8.4 months, respectively)
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

10. Tumour shrinkage by independent review (secondary endpoint)
Greater tumour shrinkage in all mutations with afatinib versus gefitinib
Tumour shrinkage by independent review (secondary endpoint)
All mutations
Afatinib
Gefitinib
Based on maximum percentage decrease from baseline in the sum of target lesion diameters.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

11. Tumour shrinkage by independent review (secondary endpoint)
Greater tumour shrinkage in Del19 mutation patients with afatinib versus gefitinib
Tumour shrinkage by independent review (secondary endpoint)
Del19 mutations
Afatinib
Gefitinib
≥20% increase
>0 - <30% decrease
≥50% decrease
≥0 - <20% increase
≥30 - <50% decrease
Based on maximum percentage decrease from baseline in the sum of target lesion diameters.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

12. Tumour shrinkage by independent review (secondary endpoint)
Greater tumour shrinkage in L858R mutation patients with afatinib versus gefitinib
Tumour shrinkage by independent review (secondary endpoint)
L858R mutations
Afatinib
Gefitinib
≥20% increase
>0 - <30% decrease
≥50% decrease
≥0 - <20% increase
≥30 - <50% decrease
Based on maximum percentage decrease from baseline in the sum of target lesion diameters.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

13. LUX-LUNG 7
Adverse events

14. Pattern of AEs consistent with the known profiles of both agents
Equally low rates of AE-related discontinuation (6.3% vs 6.3%) with differing causes; skin-related, diarrhoea and fatigue for GIOTRIF®, liver enzyme elevation and ILD for gefitinib
The most common AEs were predictable and generally manageable through supportive care and dose reduction
AE-related discontinuation
6.3%
6.3%
Afatinib
Gefitinib
AE=adverse event; ILD=interstitial lung disease.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.

15. Pattern of AEs consistent with the known profiles of both agents
Related Aes occuring in >10% patients, n(%)
Afatinib
Gefitinib
All Grades
Grade 3
Diarrhoea
144 (90.0)
19 (11.9)
97 (61.0)
2 (1.3)
Rash/Acne*
142 (88.8)
15 (9.4)
129 (81.1)
5 (3.1)
Stomatitis*
103 (64.4)
7 (4.4)
38 (23.9)
Paronychia*
89 (55.6)
3 (1.9)
27 (17.0)
1 (0.6)
Dry skin
52 (32.5)
59 (37.1)
Pruritus
37 (23.1)
36 (22.6)
Fatigue*
33 (20.6)
9 (5.6)
23 (14.5)
Decreased appetite
26 (16.3)
Nausea
22 (13.8)
Alopecia
17 (10.6)
24 (15.1)
Vomiting
6 (3.8)
ALT increase
12 (7.5)
AST increase
10 (6.3)
33 (20.8)
4 (2.5)
*Preferred terms of AEs.
4 cases of ILD with gefitinib, 3 of them ≥ grade 3, no case of ILD with GIOTRIFR. 1 case of grade 4 diarrhoea with GIOTRIF®, 1 case of grade 4 ALT with gefitinib.
ALT=alanine aminotransferase; AST=aspartate transaminase; ILD=interstitial lung disease.
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.