晚期大肠癌的个体化治疗

D
progressed
O
on 5FU, Oxaliplatin,
M
• GFR +
I
Z
E
Cetuximab + Irinotecan Irinotecan
J百度文库nker et al. AACR 2007. Abstract 3556.
7
EPIC Study Efficacy Data
PROPORTION PROGRESSION FREE
Median OS = 9.99 mo
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
MONTHS
MONTHS
biomarkers and genetic signatures
1
Story for GI at ASCO 2008
1st biomarker for individualized therapy for colorectal cancer:
KRAS status predicts responsiveness (or lack of responsiveness) to EGFR targeted therapies
Individualized Treatments for Advanced Colorectal Cancer:
The KRAS Story
David Z. Chang, MD, PhD UT MD Anderson Cancer Center
张宗圣
CSCO Annual Meeting 2008
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)
Irinotecan Capecitabine Oxaliplatin Cetuximab Bevacizumab Panitumumab
3
Some Historical Data EGFR Targeted Therapies
in CRC Cetuximab & Panitumumab
4
BOND 1: Randomized Pivotal Trial in Metastatic Colorectal Cancer
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)
➢ Cetuximab is active in 2nd line, irinotecan naïve pts
➢ Lack of overall survival: cross-over effect?
• 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
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:
2
Advances in the Treatment of Colorectal Cancer
1980 1985 1990 1995 2000 2005
5-FU
Median Survival BSC: 4-6 months 5FU: 10-14 months 5FU/OX/Iri: ~20 months + targeted therapy: >30 months?
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
0.8
HR = 0.692
0.7
95% CI = 0.617 – 0.776
0.6
0.5 STRATIFIED LOGRANK P-VALUE = < 0.0001
0.4
0.3
0.2
0.1
0.0
CETUXIMAB + IRINOTECAN; N = 648
Median OS = 10.71 mo
IRINOTECAN; N = 650
PROPORTION ALIVE
Progression Free Survival
Overall Survival
1.0 0.8 0.6
2.6 mo
0.4 0.2 0.0
4.0 mo
CETUXIMAB + IRINOTECAN; N = 648
1.0
0.9 IRINOTECAN ALONE; N = 650
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