肺癌靶向治疗进展-2012
同济大学附属上海市肺科医院肿瘤科
周彩存
Targeting the Epidermal Growth Factor Receptor
EGFR突变: EGFR TKI一线首选
西妥昔单抗在晚期NSCLC治疗中地
位?
SELECT
第二代EGFR TKI有效
LUX-Lung 3
PF-299
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Supplementary analysis: influence of
EGFR TKI and chemotherapy on OS
Patients at risk
Patients receiving
chemo only* 21 17 12 8 6 4 3 0
Patients receiving
EGFR TKI only‡ 33 32 27 24 17 12 7 0
Patients receiving
EGFR TKI and chemo§ 94 94 89 80 68 60 28 6
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Patients receiving EGFR TKI and chemo vs
patients receiving chemo only p=0.0001
Patients receiving EGFR TKI only vs patients
receiving chemo only p=0.057
Log-rank p value <0.0001
n
Events
n (%)
Median
(months) 95% CI
Received chemo
only* 21 17 (81) 11.70 7.29–22.87
Received EGFR
TKI only‡ 33 22 (67) 20.67 16.62–28.32
Received EGFR
TKI and chemo§ 94 50 (53) 30.39 25.99–NR
*Chemo only, no EGFR TKI: patients from the GC arm who had no further treatment (n=16) or further chemotherapy (n=5)
‡EGFR TKI only, no chemo: patients from the erlotinib arm who are still on treatment (n=7), had no further treatment (n=25) and who were re-challenged (n=1)
§EGFR TKI and chemo: patients from the erlotinib arm who switched to chemo (n=43), patients from the GC arm who switched to erlotinib in any line (n=51)
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Primary endpoint: PFS
Independent review ‒
all randomized patients
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Number at risk
Afatinib 230 180 151 120 77 50 31 10 3 0
Cis/Pem 115 72 41 21 11 7 3 2 0 0
Progression-free survival (months)
0 3 6 9 12 15 18 21 24 27
Afatinib
n=230
Cis/pem
n=115
PFS event, n (%) 152 (66) 69 (60)
Median PFS (months) 11.1 6.9
Hazard ratio
(95% confidence interval)
0.58 (0.43–0.78)
P=0.0004
47%
22%
Yang JC, et al.
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Number at risk
Afatinib 204 169 143 115 75 49 30 10 3 0
Cis/Pem 104 62 35 17 9 6 2 2 0 0
Progression-free survival (months)
0 3 6 9 12 15 18 21 24 27
Afatinib
n=204
Cis/pem
n=104
PFS event, n (%) 130 (64) 61 (59)
Median PFS (months) 13.6 6.9
Hazard ratio
(95% confidence interval)
0.47 (0.34–0.65)
P<0.0001
PFS: Common mutations (Del19/L858R)
Independent review – patients with Del 19/L858R (n=308)
Yang JC, et al.
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First-line dacomitinib (PF-00299804), an irreversible
pan-HER tyrosine kinase inhibitor for patients with
EGFR-mutant lung cancer
MG Kris, Mok , SHI Ou, et al.
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Benjamin Besse. ASCO 2012
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Conclusions
第一代,二代EGFR TKI治疗EGFR突变晚期NSCLC有效
较好的PFS,缓解率,生存质量与安全性
OS无差异
第二代EGFR TKI有少见EGFR突变似乎有效
第二代TKI不良反应>第一代TKI
西妥昔单抗联合二线化疗:无效
第二代耐药机制: T790M,c-MET扩增?
结论
NSCLC是由不同驱动基因突变的NSCLC所组
成
MEK抑制剂联合化疗对KRAS突变NSCLC可
能有效
ALK耐药机制多种多样,并且可以druggable
抗血管生成的小分子抑制剂联合化疗在晚期
NSCLC未见疗效
肺癌靶向治疗进展-2012
幻灯片编号 2
幻灯片编号 3
幻灯片编号 4
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Supplementary analysis: influence of EGFR TKI and chemotherapy on OS
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Primary endpoint: PFS �Independent review ‒ all randomized patients
PFS: Common mutations (Del19/L858R)�Independent review – patients with Del 19/L858R (n=308)
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幻灯片编号 12
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结论