until tumour progression until tumour progression
DESCRIPTION
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 questionnairesTRANSCRIPT
• 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
afatinib
40 mg oral once dailyuntil tumour progression
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.
LUX Lung 7 Clinical Trial
Median follow-up: 27.4 months
• 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)
• 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
Primary endpoints
Secondary endpoints included
LUX Lung 7 Study Endpoints
3
Recruitment: Dec 2011-Aug 2013
Germany 14
Spain 25
France 34
Norway 3
Sweden 14
UK 7
Ireland 9
China 48
Hong Kong 6
Taiwan 22
Korea 56
Singapore 27
Australia 19
Canada 31
LUX Lung 7: 64 sites in 14 countries
Afatinib160, N (%)
Gefitinib159, N (%)
Total319, N (%)
Age, median yrs (min-max) 63 (30-86) 63 (32-89) 63 (30-89)
GenderFemale 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) 106 (66.7) 212 (66.5)
Baseline ECOG 0 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 mutationDel19# 93 (58.1) 93 (58.4) 186 (58.3)
L858R 67 (41.9) 66 (41.6) 133 (41.7)
Patient demographics and characteristics were well balancedbetween the 2 treatment arms
LUX-LUNG 7
Efficacy
6
Afatinib demonstrated a 27% reduction in relative risk of death or progression compared to gefitinib
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.
• Patients twice as likely to be alive and progression free at 2 years with afatinib vs gefitinib (18% vs 8%, respectively)
Progression-free survival by independent review (primary endpoint)
Estim
ated
PFS
pro
babi
lity
0.2
0.4
0.6
0.8
1.0
0.0
Time of progression free survival (months)
0 3 6 9 18 2112 15 24 42
Hazard ratio 0.73(95% CI, 0.57-0.95)P=0.0165
Afatinib® (n=160)Gefitinib (n=159)
18%vs 8%
Median (months)
11.010.9
27 30 33 36 39
27%vs 15%
7
Afatinib – PFS benefit consistent across subgroups,including EGFR mutation type
Park K et al. Abstract LBA2 and oral presentation. European Society for Medical Oncology (ESMO) ASIA, Singapore, 20th December 2015.
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
0 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)
Factors Hazard ratio (95% Cl)Number of patients
Favours afatinib Favours gefitinib1/4 1 4 161/16
Progression-free survival by independent review (primary endpoint) prespecified subgroups
8
Patients remained on treatment significantly longer with afatinib than with gefitinib
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.
• 27% significant reduction in relative risk of treatment failure vs gefitinib (P=0.0073)
• Overall survival data not yet mature
Estim
ated
pro
babi
lity
of b
eing
free
of
trea
tmen
t fai
lure
0.2
0.4
0.6
0.8
1.0
0.0
Time to treatment failure (months)
0 3 6 9 18 2112 15 24 42
Hazard ratio 0.73(95% CI, 0.58-0.92)P=0.0073
Afatinib® (n=160)Gefitinib (n=159)
Median (months)
13.711.5
27 30 33 36 39
Time to treatment failure (primary endpoint)
9
Afatinib demonstrated significantly improved response rates vsgefitinib
• 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.
Objective response by independent review (secondary endpoint)
P=0.0083
0%
20%
40%
60%
80%70%
56%
Obj
ectiv
e re
spon
se ra
te (%
)
Afatinib Gefitinib
Greater tumour shrinkage in all mutations with afatinib versus 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.
All mutationsTumour shrinkage by independent review (secondary endpoint)
-100
-80
-60
-40
-20
0
20
40
Max
imum
dec
reas
e fr
om b
asel
ine
(%)
Afatinib
Gefitinib
11
Greater tumour shrinkage in Del19 mutation patients with afatinib versus 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.
Del19 mutationsTumour shrinkage by independent review (secondary endpoint)
-100
-80
-60
-40
-20
0
20
40
Max
imum
dec
reas
e fr
om b
asel
ine
(%)
-100
-80
-60
-40
-20
0
20
40
Max
imum
dec
reas
e fr
om b
asel
ine
(%)
Afatinib Gefitinib
≥20% increase
≥0 - <20% increase
>0 - <30% decrease
≥30 - <50% decrease
≥50% decrease
12
Greater tumour shrinkage in L858R mutation patients with afatinib versus 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.
L858R mutationsTumour shrinkage by independent review (secondary endpoint)
-100
-80
-60
-40
-20
0
20
40
Max
imum
dec
reas
e fr
om b
asel
ine
(%)
Afatinib Gefitinib
≥20% increase
≥0 - <20% increase
>0 - <30% decrease
≥30 - <50% decrease
≥50% decrease
-100
-80
-60
-40
-20
0
20
40
Max
imum
dec
reas
e fr
om b
asel
ine
(%)
LUX-LUNG 7
Adverse events
13
14
• 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 supportivecare and dose reduction
Pattern of AEs consistent with the known profiles ofboth agents
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.
AE-related discontinuation
0%
5%
10%
15%
Obj
ectiv
e re
spon
se ra
te (%
)
Afatinib Gefitinib
6.3% 6.3%
15
Pattern of AEs consistent with the known profiles ofboth agents
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.
*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.
Related Aes occuringin >10% patients, n(%)
Afatinib Gefitinib
All Grades Grade 3 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) 1 (0.6) 19 (11.9)
Nausea 26 (16.3) 2 (1.3) 22 (13.8)
Alopecia 17 (10.6) 24 (15.1)
Vomiting 17 (10.6) 6 (3.8) 1 (0.6)
ALT increase 15 (9.4) 38 (23.9) 12 (7.5)
AST increase 10 (6.3) 33 (20.8) 4 (2.5)