• Chemonaïve
• Age ≥18 years
• Adenocarcinoma histology
• Never or light exsmokers*
• Life expectancy ≥12 weeks
• PS 0-2
• Measurable stage IIIB / IV disease
FLEX : 1st-cycle rash CT + Erbitux
Secondary endpoints
Any grade (n=290)
Grade 0 (n=228)
Gefitinib Carboplatin Paclitaxel
1200 PE: exceeded
Pemetrexed Bevavizumab Cetuximab EGFR-TKI
IPASS: Gefitinib vs Carbo/Pac in advanced NSCLC
Endpoints
Patients
(200 mg / m2) 3 weekly#
Exploratory
• Biomarkers
• EGFR mutation
• EGFR-gene-copy number
• EGFR protein expression
• *Never smokers, <100 cigarettes in lifetime; light ex-smokers, stopped 15 years ago and smoked
2-arms 1st-line
PFS
EGFR突变 患Ge者fitin从ib 易瑞沙 Carb治op疗lati中n Pa高clit度axe获l 益
1200
PE: exceeded
EGFR-TKI
FLEX : 1st-cycle rash CT + Erbitux
Gatzemeier et al. JTO 3, 11, 4, (Abstr. 8), 2008
Carboplatin / paclitaxel EGFR M+
(n=129)
Carboplatin / paclitaxel EGFR M-
(n=85)
Gefitinib, HR=0.19,
Байду номын сангаас
95% CI 0.13, 0.26, p<0.0001
No. events M+ = 97 (73.5%)
No. events M- = 88 (96.7%)
Gefitinib (250 mg / day)
1:1 randomisation Carboplatin (AUC 5 or 6) / paclitaxel
Primary
• Progression-free survival (non-inferiority)
Secondary
• Objective response rate • Overall survival • Quality of life • Disease-related symptoms • Safety and tolerability
1700 PE: met
AVAiL
4-arms 1st-line PFS
Bevacizumab Gemcitabine Cisplatin
1043 PE: met
FLEX
2-arms 1st-line OS
Cetuximab Vinorelbine Cisplatin
1100 PE: met
IPASS
非小细胞肺癌治疗进展
Competition in NSCLC
Design
Primary endpoint Agents
No. of Pts. Outcome
JMDB
2- arms 1st-line OS
Pemetrexed Gemcitabine Cisplatin
1700 PE: met
AVAiL
Mok et al ESMO LBA 2, 2008
IPASS: Comparison of PFS by mutation status within treatment arms
Probability 1.0 of PFS
0.8
0.6
0.4
Gefitinib EGFR M+ (n=132)
Gefitinib EGFR M- (n=91)
Carboplatin / paclitaxel, HR=0.78,
95% CI 0.57, 1.06, p=0.1103
No. events M+ = 111 (86.0%)
No. events M- = 70 (82.4%)
0.2
结论：EGFR突变的患者选择EGFR-TKIs治疗
0.0
EGFR状态未知的患者选择化疗 0
10 pack years; #limited to a maximum of 6 cycles
Carboplatin / paclitaxel was offered to gefitinib patients upon progression
PS, performance status; EGFR, epidermal growth factor receptor
Mok et al ESMO LBA 2, 2008
Competition in NSCLC
Design
Primary endpoint Agents
No. of Pts. Outcome
JMDB
2- arms 1st-line OS
Pemetrexed Gemcitabine Cisplatin
4
8
12
16
20
24
Time from randomisation (months)
Hazard ratio <1 implies a lower risk of progression in the M+ group than in the M- group
M+, mutation positive; M-, mutation negative
4-arms 1st-line PFS
Bevacizumab Gemcitabine Cisplatin
1043 PE: met
FLEX
2-arms 1st-line OS
Cetuximab Vinorelbine Cisplatin
1100 PE: met
IPASS
2-arms 1st-line PFS