massimo zeuli oncologia medica a istituto regina elena roma zeuli@ifo.it zeuli@ifo.it "the best...
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Massimo Zeuli Oncologia Medica AIstituto Regina ElenaRoma
zeuli@ifo.it
"The best therapeutic approach to patients with KRAS wild type tumors"
Roma 4 marzo 2011
EGFR-Targeted Monoclonal Antibodies in mCRC
• Cetuximab– IgG1 mAb
– Chimeric protein
• Panitumumab[1]
– IgG2 mAb
– Fully humanized
• Role of Kirsten-ras (K-ras) mutation
1. Yang XD, et al. Crit Rev Oncol Hematol. 2001;38:17-23.
HR: 0.54 (95% CI: 0.42-0.71)
P < .0001
Time to Progression
HR: 0.91 (95% CI: 0.68-1.21)
P = .48
OS
• Addition of cetuximab to irinotecan improved the response rate and time to progression but not overall survival
0
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0 2 4 6 8 10 12
Pro
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ssio
n F
ree
(%)
00 2 4 6 8 10 12 14 16
MonthsMonths
Aliv
e (%
)
Cunningham D, et al. N Engl J Med. 2004;351:337-345. Copyright © 2004 Massachusetts Medical Society. All rights reserved.
The BOND Study: Survival Data
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Months
Pro
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ssio
n F
ree
(%)
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0 3 6 9 12 15 18
HR: 0.69 (95% CI: 0.62-0.78)P ≤ .0001
Cetuximab + irinotecan (n = 648)Irinotecan (n = 650)
Median PFS: 4.0 months
Median PFS:
2.6 months
Sobrero AF, et al. EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients With Metastatic Colorectal Cancer.J Clin Oncol. 2008;26:2311-2319. Reprinted with permission from the American Society of Clinical Oncology
EPIC Study of Cetuximab in Second-Line mCRC: PFS
Van Cutsem E, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer.J Clin Oncol. 2007;25:1658-1664. Reprinted with permission from the American Society of Clinical Oncology.
Eve
nt
Fre
e (
%)_
0
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Weeks0 8 16 24 32 40 48 56
HR: 0.54 (95% CI: 0.44-0.66)P < .0001
Panitumumab + BSC (n = 231)BSC (n = 232)
Panitumumab vs BSC in EGFR-Positive CRC: PFS Results
Amado R, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.J Clin Oncol 2008;26:1626-1634. Reprinted with permission from the American Society of Clinical Oncology.
2 4 6 8 10 12 14 16 18
Median PFS:
7.3 weeks
Median PFS: 12.3 weeks
Pro
gre
ss
ion
Fre
e (
%)
Weeks
0
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0 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52
HR: 0.45 (95% CI: 0.34-0.59)P < .0001
Panitumumab + BSC (n = 124)
BSC (n = 119)
Panitumumab vs BSC in mCRC With Wild-Type K-ras: PFS Results
Weeks2 4 6 8 10 12 14 16 18
Median PFS:
7.3 weeks
Median PFS: 7.4 weeks
Pro
gre
ss
ion
Fre
e (
%)
0
10
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0 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52
HR: 0.99 (95% CI: 0.73-1.36)
Panitumumab + BSC (n = 84)
BSC Alone (n = 100)
Amado R, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.J Clin Oncol 2008;26:1626-1634. Reprinted with permission from the American Society of Clinical Oncology.
Panitumumab vs BSC in mCRC With Mutant K-ras: PFS Results
Douillard J et al. JCO 2010;28:4697-4705
Pazienti kras wild type Cetuximab/Panitumumab aumentano l’efficacia
del trattamento chemioterapico
Pazienti kras wild type
Cetuximab/Panitumumab aumentano l’efficacia del trattamento chemioterapico
Bevacizumab aumenta l’efficacia del trattamento chemioterapico
Pozzo C. et al Cancer Treat Rev, 2008
Which regimen should we use as neoadjuvant treatment for liver metastases?
* Of the 37 patients evaluable fortumour KRAS mutation status, 81% had KRAS wild-type tumours.
*
Resection rates following targeted therapies plus chemotherapy in randomized trials
Van Cutsem E, et al. N Engl J Med 2009 Bokemeyer C, et al. J Clin Oncol 2009;27:663–671
Saltz LB et al. J Clin Oncol 2008
FOLFOX + ERBITUX
FOLFOX
FOLFIRI + ERBITUX
FOLFIRI
FOLFOX/XELOX+ bevacizumab
FOLFOX + XELOX
NO
1696
6 L
LD
CR
YS
TA
L
LL
DO
PU
S K
RA
S w
t
0 2 4 6 8 10 12 14
p=NS
Patients (%)
R0 resection rate
9.8
4.1
9.8
4.5
12.3
11.6
Pazienti kras wild type
Cetuximab/Panitumumab aumentano l’efficacia del trattamento chemioterapico
Bevacizumab aumenta l’efficacia del trattamento chemioterapico
Cetuximab aumenta la percentuale di resezioni epatiche R0?
Massimo Zeuli Oncologia Medica AIstituto Regina ElenaRoma
zeuli@ifo.it
"The best therapeutic approach to patients with KRAS wild type tumors"
Roma 4 marzo 2011
?
Pazienti k-ras wild-type, chrono-IFLO+ Cetuximab (Studio POCHER Br J Cancer 2010). I pazienti che non possono essere trattati con questo schema e sono wild-type ricevono in prima linea FOLFIRI + Cetuximab (Studio Crystal N Engl J Med 2009).
FOLFOX4 x 3 mesi Chirurgia FOLFOX4 x 3 mesi(studio EPOC - Lancet 2008):
C: Gruppo “ NON- RESECTABLE”
K-ras Wild Type
K-ras Mutant
1° Linea FOLFIRI + BEVA
FOLFIRI + BEVA
II° Linea FOLFOX FOLFOX
III° Linea Panitumumab MMC + fluoro pirimidina*
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