晚期大肠癌的个体化治疗

• N=463 • Patients
third-line mCRC • EGFR expression required
0.8
HR = 0.692
0.7
95% CI = 0.617 – 0.776
0.6
0.5 STR ATIFIED LO G R AN K P-VALUE = < 0.0001
0.4
0.3
0.2
0.1
0.0
CETUXIM AB + IRINOTECAN; N = 648 M edian OS = 10.71 m o
8.9
46.9%
Irinotecan (N=609)
8
38.7%
P Value
< 0.036 < 0.005
➢ Cetuximab improves RR, PFS in 1st line, in combination with FOLFIRI
10
Phase III Study: Panitumumab vs Best Supportive Care
MONTHS
MONTHS
➢ Cetuximab is active in 2nd line, irinotecan naïve pts
➢ Lack of overall survival: cross-over effect?
8
CRYSTAL: Phase III Trial of FOLFIRI +/- Cetuximab in First-line mCRC
P R O P O R T IO N A L IV E
Progression Free Survival
Overall Survival
1.0 0.8 0.6
2.6 m o
0.4 0.2 0.0
4.0 m o
CETUXIM AB + IRINO TEC AN ; N = 648
1.0
0.9 IRINO TEC AN ALO NE; N = 650
R
A
N
D
O
• First-line
mCRC
M
I
Z
E
FOLFIRI + cetuximab (608)
FOLFIRI (609)
Cutsem et aI, et al. ASCO 2007. 4000. 9
CRYSTAL Efficacy Data
PFS
Response Rate (%)
Cetuximab +FOLFIRI (N=608)
E
Histamine receptor antagonist premedication given
before at least the first cetuximab infusion.
Cunningham D, et al. N Engl J Med. 2004;351:337-345.
5
Cetuximab Randomized Pivotal Trial: Response Rates
N
weekly infusion 250 mg/m2) +
irinotecan (same as prestudy therapy)
D
(n=218)
O
M
Cetuximab
I
(initial dose, 400 mg/m2 then weekly
Z
infusion 250 mg/m2) (n=111)
D
progressed
O
on 5FU, Oxaliplatin,
M
• GFR +
I
Z
E
Cetuximab + Irinotecan Irinotecan
Jonker et al. AACR 2007. Abstract 3556.
7
EPIC Study Efficacy Data
P R O P O R T IO N P R O G R E S S IO N F R E E
biomarkers and genetic signatures
1
2
Байду номын сангаас
3
Some Historical Data EGFR Targeted Therapies
in CRC Cetuximab & Panitumumab
4
BOND 1: Randomized Pivotal Trial in Metastatic Colorectal Cancer
Cunningham D, et al. N Engl J Med. 2004;351:337-345.
6
EPIC: Cetuximab + Irinotecan vs Irinotecan as 2nd-line Therapy
R
A
• N=1298
N
• Patients with CRC who
晚期大肠癌的个体化治疗
0
SUMMARY
• Targeted therapies have improved clinical outcome of mCRC
• Need judicious use of these agents: when, how • Many questions remaining • How to overcome the high cost ► Treatments need to be individualized:
• N=329 • Patients with
mCRC who progressed during or within 3 mo after irinotecan • EGFR+ CRC
R
Cetuximab + irinotecan
A
Cetuximab (initial dose, 400 mg/m2 then
Objective Response Rate
10.8%
22.9% P=0.007
Median Duration of Response
5.7 mo 4.2 mo
0 5 10 15 20 25
0 123456 Cetuximab with irinotecan (n=218) Cetuximab as a single agent (n=111)
IRINOTECAN; N = 650 M edian OS = 9.99 m o
HR = 0.975 (95.03% CI = 0.854 – 1.114)
STRATIFIED LOGRANK P-VALUE = 0.7115
0
3
6
9
12
15
18
0 3 6 9 12 15 18 21 24 27 30 33 36 39