Transcript Eric Van Cutsem

Forging a new standard
in metastatic CRC
Eric Van Cutsem
University Hospital Gasthuisberg
Leuven, Belgium
Advances in the treatment
of mCRC
1980
1985
1990
1995
2000
2005
2010
Best supportive care
5-FU
Irinotecan
Capecitabine
Oxaliplatin
Bevacizumab
and EGFR inhibitors
35
30
Months
25
20
15
10
Median OS
5
0
1980
1985
1990
1995
2000
2005+
mCRC = metastatic colorectal cancer; 5-FU = 5-fluorouracil; MoAbs = monoclonal antibodies;
OS = overall survival
Capecitabine combinations are effective
in the metastatic setting
CAPOX
first line
(n=80)
CAPIRI
second line
(n=34)
CAPIRI
first line
(n=77)
CAPOX
second line
(n=31)
ORR (%)
51
21
41
13
PFS (months)
6.2
5.2
7.1
4.3
OS (months)
16.5
12.9–18.5
18.8
15.7–23.7
 CAPOX: capecitabine 1,000mg/m2 b.i.d. day 1–14 plus oxaliplatin
70mg/m2 day 1, 8 every 3 weeks
 CAPIRI: capecitabine 1,000mg/m2 b.i.d. day 1–14 plus irinotecan
80–100mg/m2 day 1, 8 every 3 weeks
ORR = overall response rate
PFS = progression-free survival
b.i.d. = twice daily
Grothey A, et al. J Clin Oncol 2004;22:254 (Abstract 3534)
Efficacy of capecitabine versus 5-FU/LV:
meta-analysis of survival in six clinical trials
Median OS, months
(95% CI)
Hazard ratio (HR)
(95% CI)
5-FU-based
regimens
(n=3,074)
Capecitabine-based
regimens
(n=3,097)
22.5
23.1
(21.3–23.5)
(22.1–24.4)
0.96
0.90–1.02
Capecitabine is therapeutically noninferior to 5-FU/LV
in patients with colorectal or gastric cancer
CI = confidence interval
Cassidy J, et al. Presented at ASCO GI 2008 (Abstract 340)
Bevacizumab adds strong benefit
to all regimens
5-FU/LV
PFS
+ bevacizumab
OS
IFL
+ bevacizumab
FOLFOX
+ bevacizumab
FOLFIRI
+ bevacizumab
FOLFOX/FOLFIRI
+ bevacizumab
0
5
10
15
Months
20
25
LV = leucovorin; IFL = irinotecan, 5-FU, leucovorin; FOLFOX = leucovorin, 5-FU, oxaliplatin
FOLFIRI = leucovorin, 5-FU, irinotecan
30
Linking the mechanism of action of
bevacizumab with clinical benefit in mCRC
EARLY EFFECTS
1
Regression
Decrease tumour
size
2
Normalisation
Improve delivery of
chemotherapy
CONTINUED EFFECTS
3
Inhibition
Suppress new vessel growth
Suppress regrowth via
vessel ‘scaffolds’
Enable metastasectomy
Increase PFS
Increase OS
Irinotecan-containing regimens
with bevacizumab
and/or capecitabine
AVF2107g: bevacizumab plus first-line
IFL: superior PFS plus OS
Median PFS
6.2 vs 10.6 months
HR=0.54 (p<0.0001)
1.0
Median OS
15.6 vs 20.3 months
HR=0.66 (p<0.001)
1.0
IFL + bevacizumab
0.8
IFL + placebo
OS estimate
PFS estimate
0.8
IFL + bevacizumab
0.6
0.4
0.2
IFL + placebo
0.6
0.4
0.2
6.2
0
0
10.6
10
20
Months
15.6
0
30
0
10
20.3
20
Months
30
40
Hurwitz H, et al. N Engl J Med 2004;350:2335–42
Bevacizumab plus FOLFIRI has been
evaluated in several phase II trials
BICC-C1
Samelis2
Kopetz3
Treatment
regimen
FOLFIRI or mIFL +
bevacizumab
Bevacizumab
+ IFL
Bevacizumab
+ FOLFIRI
Indication
First-line
Second-line
First-line
Primary
endpoint
PFS
Not available
PFS
Study
1Fuchs
mIFL = irinotecan,
5-FU, leucovorin
CS, et al. J Clin Oncol 2007;25:4779–86
GF, et al. ASCO GI Cancers Symposium 2007 (Abstract 394)
3Kopetz S, et al. ASCO GI Cancers Symposium 2007 (Abstract 4089)
2Samelis
Phase IV trial of bevacizumab plus
FOLFIRI (AVIRI): study design
Patients with previously
untreated, unresectable
mCRC
(n=209)
Bevacizumab + FOLFIRI
 The largest trial of bevacizumab plus FOLFIRI
 International multicentre trial: 31 centres
 Primary endpoint: PFS
 Secondary endpoints: OS, ORR and safety
 Treatment until progression or unacceptable toxicity
Ackland S, et al. Presented at ASCO GI 2008 (Abstract 463)
AVIRI: efficacy summary
(ITT population)
Parameter
n=209
Median PFS, months (95% CI)
11.1 (10.3–12.1)
Median OS, months (95% CI)
22.2 (20.5–25.9)
ORR (%)
Complete response (CR)
Partial response (PR)
53.1
3.8
49.3
Stable disease (SD) (%)
32.5
Progressive disease (PD) (%)
Disease control rate (%)
7.7
85.6
Median PFS and OS is comparable to that observed with
bevacizumab plus IFL in the pivotal AVF2107g trial
ITT = intent to treat
Ackland S, et al. Presented at ASCO GI 2008 (Abstract 463)
AVIRI: safety summary
Selected grade 3–5 adverse event (AE)
n=209 (%)
Bleeding
4
Hypertension
5
Proteinuria
2
Arterial thromboembolism event (ATE)
4
Gastrointestinal (GI) perforation
2
Wound-healing complications
<1
The safety profile of bevacizumab plus FOLFIRI
is consistent with that reported for bevacizumab
plus other standard chemotherapy regimens
Ackland S, et al. Presented at ASCO GI 2008 (Abstract 463)
BICC-C: bevacizumab plus
irinotecan-based chemotherapy
R
Initial design
Amended design
FOLFIRI
(n=144)
Bevacizumab +
FOLFIRI (n=60)
mIFL
(n=141)
n=430
CAPIRI
(n=145)
R
n=117
Bevacizumab + mIFL
(n=57)
Protocol amended due
to approval of
bevacizumab
Primary endpoint: PFS
Fuchs CS, et al. J Clin Oncol 2007;25:4779–86
BICC-C: bevacizumab plus irinotecanbased chemotherapy – efficacy
Before protocol
amendment
Regimen
Efficacy
Median PFS (months)
FOLFIRI
mIFL
CAPIRI
After protocol
amendment
Bevacizumab +
FOLFIRI
mIFL
7.6
5.9
5.8
Median OS (months)
23.1
17.6
18.9
28
19.2
ORR (%)
47
43
39
58
53
11.2
8.3
 Preliminary data suggest that FOLFIRI plus bevacizumab has
superior efficacy to mIFL plus bevacizumab
– results are comparable to those reported in AVF2107g
Fuchs CS, et al. J Clin Oncol 2007;25:4779–86
Fuchs CS, et al. J Clin Oncol 2007;26:689–90
Bevacizumab plus FOLFIRI in first-line
mCRC: impact on PFS
Tournigand
FOLFIRI
n=109
BEAT
FOLFIRI + bevacizumab
n=504
BRiTE
FOLFIRI + bevacizumab
n=280
AVIRI
FOLFIRI + bevacizumab
n=209
Kopetz
FOLFIRI + bevacizumab
n=41
BICC-C
FOLFIRI + bevacizumab
n=57
0
2.5
5.0
7.5
Months
10.0
12.5
15.0
Tournigand C, et al. J Clin Oncol 2004;22:229–37
Berry S, Van Cutsem E, et al. Eur J Cancer Suppl 2007;5:241 (Abstract P#3020)
Kozloff M, et al. Presented at ASCO GI 2007 (Abstract 375)
Sobrero A, et al. Eur J Cancer Suppl 2007;5:254 (Abstract P#3060)
Kopetz S, et al. Presented at ASCO GI 2007 (Abstract 4089)
Fuchs CS, et al. J Clin Oncol 2007;25:4779–86
Oxaliplatin-containing regimens
with bevacizumab
and/or capecitabine
E3200: bevacizumab second line:
superior PFS plus OS with FOLFOX4
Median PFS
4.7 vs 7.3 months
HR=0.61 (p<0.0001)
1.0
0.8
Median OS
10.8 vs 12.9 months
HR=0.75 (p=0.0011)
1.0
0.8
FOLFOX4 + bevacizumab
FOLFOX4 + bevacizumab
FOLFOX4
OS estimate
PFS estimate
FOLFOX4
0.6
0.4
0.2
0.6
0.4
0.2
4.7
7.3
0
10.8
12.9
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Months
0 3
6
9 12 15 18 21 24 27 30 33 36
Months
Giantonio BJ, et al. J Clin Oncol 2007;25:1539–44
CAPOX is equivalent to FOLFOX
in phase II/III studies
ORR (%)
n
PFS (months)
OS (months)
CAPOX FOLFOX CAPOX FOLFOX CAPOX FOLFOX
AIO1
476
47
54
7.1
8.0
16.8
18.2
TTD2
348
37
46
8.9
9.5
18.1
20.8
ML169873
306
42
46
8.8
9.3
19.9
20.5
NO169664,5 2,034
46
49
8.0
8.5
19.8
19.6
17.5
4.7
4.8
11.9
12.6
33
6.4
6.2
—
—
NO169676
627 20.1
SICOG04017 322
1Porschen
34
R, et al. J Clin Oncol 2007;25:4217–23; 2Díaz-Rubio E, et al. J Clin Oncol
2007;25:4224–30; 3Ducreux M, et al. J Clin Oncol 2007;25(Suppl. 18):170s (Abstract 4029)
4Cassidy J, et al. ASCO GI 2007 (Abstract 270); 5Cassidy J, et al. J Clin Oncol 2007;25(Suppl. 18)
(Abstract 4030); 6Rothenberg ML, et al. J Clin Oncol 2007;25(Suppl. 18):171s (Abstract 4031);
7Comella P, et al. Presented at ASCO GI 2008 (Abstract 344)
Phase II trial of first-line bevacizumab plus
CAPIRI or CAPOX (AIO): study design
Previously untreated
mCRC
(n=255)
CAPOX + bevacizumab
7.5mg/kg every 3 weeks
PD or
toxicity
CAPIRI + bevacizumab
7.5mg/kg every 3 weeks
PD or
toxicity
 Treatment (3-week cycle)
– patients in arm A receive bevacizumab 7.5mg/kg (day 1)
plus oxaliplatin 130mg/m2 (day 1) and capecitabine
1,000mg/m2 (b.i.d. day 1–14)
– patients in arm B receive bevacizumab 7.5mg/kg (day 1)
plus irinotecan 200mg/m2 (day 1) and capecitabine
800mg/m2 (b.i.d. day 1–14)
PD = progressive disease
Schmiegel WH, et al. J Clin Oncol
2007;25(Suppl. 18):172s (Abstract 4034)
Phase II trial of first-line bevacizumab
plus CAPIRI or CAPOX (AIO): efficacy
Bevacizumab + Bevacizumab
CAPOX
+ CAPIRI
(n=118)
(n=112)
Outcome (%)
ORR
CR
PR
45
5
40
47
4
43
SD
28
23
Progression-free at 6 months
74
80
Schmiegel WH, et al. J Clin Oncol 2007;25 (Suppl. 18):172s (Abstract 4034)
Phase II trial of first-line bevacizumab
plus CAPIRI or CAPOX (AIO): safety
Bevacizumab +
CAPOX (n=117)
16
13
6
Bevacizumab +
CAPIRI (n=112)
13
0
4
Vomiting
3
4
Fever
Neutropenia
Thrombocytopenia
1
2
4
0
4
0
Fatigue
2
2
Ileus
Alopecia
2
0
1
1
Grade 3/4 AE (%)
Diarrhoea
Sensory neuropathy
Hand-foot syndrome
 CAPIRI and CAPOX have similar safety when combined with bevacizumab
Schmiegel WH, et al. J Clin Oncol 2007;25 (Suppl. 18):172s (Abstract 4034)
Phase III trial of CAPOX/FOLFOX4 ±
bevacizumab (NO16966): study design
Recruitment
June 2003 – May 2004
Recruitment
February 2004 – February 2005
CAPOX
(n=317)
CAPOX +
placebo
(n=350)
CAPOX +
bevacizumab
(n=350)
FOLFOX4
(n=317)
FOLFOX4 +
placebo
(n=351)
FOLFOX4 +
bevacizumab
(n=349)
Initial two-arm
open-label study
(n=1,000)
Protocol amended to 2 x 2 placebo-controlled
design after bevacizumab phase III data became
available (n=1,400)
 Primary endpoints
– at least equivalent PFS with CAPOX versus FOLFOX4
– superior PFS with bevacizumab plus CAPOX/FOLFOX4 versus
CAPOX/FOLFOX4
Saltz L, et al. J Clin Oncol 2007;25 (Suppl. 18):170s (Abstract 4028)
NO16966: PFS – chemotherapy plus
bevacizumab (general and on-treatment
populations)
1.0
FOLFOX4 or CAPOX + bevacizumab
FOLFOX4 or CAPOX + placebo
PFS estimate
0.8
On treatment: HR=0.63
(97.5% CI: 0.52–0.75)
p<0.0001
0.6
General: HR=0.83
(97.5% CI: 0.72–0.95)
p=0.0023
0.4
0.2
0
0
5
10
15
20
PFS (months)
 Bevacizumab-containing arm: separation occurs between the PFS for general
versus on-treatment populations after 6 months (vertical arrow)
Saltz L, et al. J Clin Oncol 2007;25(Suppl. 18):170s (Abstract 4028)
NO16966: bevacizumab first-line –
PFS plus OS with CAPOX/FOLFOX4
Median PFS
8.0 vs 9.4 months
HR=0.83 (p=0.023)
1.0
Median OS
19.9 vs 21.2 months
HR=0.89 (p=0.0769)
1.0
CAPOX/FOLFOX4 +
bevacizumab
CAPOX/FOLFOX4 +
placebo
CAPOX/FOLFOX4 +
placebo
0.8
OS estimate
0.8
PFS estimate
CAPOX/FOLFOX4 +
bevacizumab
0.6
0.4
0.2
0.6
0.4
0.2
8.0
9.4
0
19.9
0
0
5
10
15
Months
20
25
0
6
12
21.2
18
24
30
36
Months
Saltz L, et al. Proc World Congress on Gastrointestinal Cancer
2007 (Abstract O-0032)
NO16966: efficacy results for superiority –
major points
 Bevacizumab provides significant/superior PFS when
added to oxaliplatin-based chemotherapy regimens
 Treatment until progression is crucial to demonstrate
full potential of bevacizumab
 Analyses of withdrawal data and PFS on treatment
show excellent efficacy for bevacizumab
 IRC analysis clearly demonstrates superior PFS for
bevacizumab in all treatment groups
IRC = independent review committee
NO16966: bevacizumab is well tolerated
when combined with oxaliplatin- or
capecitabine-based regimens
F O L F O X 4 /C A P O X +
p la c e b o
n = 6 7 5 (% )
G ra d e 3 /4 A E
F O L F O X 4 /C A P O X +
b e va c iz u m a b
n = 6 9 4 (% )
A n y g ra d e 3 /4 A E
75
80
G I p e rfo ra tio n s
<1
<1
B le e d in g
1
2
ATE
1
2
H yp e rte n s io n
1
4
P ro te in u ria
–
<1
W o u n d -h e a lin g c o m p lic a tio n
<1
<1
D is c o n tin u a tio n s d u e to a n a d v e rs e
e ve n t
21
31
A ll-c a u s e 6 0 -d a y m o rta lity
1 .6
2
T re a tm e n t-re la te d m o rta lity u p to 2 8
d a ys a fte r la s t d o s e
1 .5
2
Saltz L, et al. J Clin Oncol 2007;25 (Suppl. 18):170s (Abstract 4028)
Bevacizumab in the clinical setting
Data from BEAT and BRiTE
Bevacizumab plus first-line chemotherapy
in clinical practice: BEAT and BRiTE
BEAT1
Patients with previously
untreated, unresectable
mCRC
(n=1,914)
Bevacizumab +
chemotherapy
PD
Bevacizumab +
chemotherapy
PD
BRiTE2
Patients with previously
untreated, unresectable
mCRC
(n=1,953)
1Berry
S, Van Cutsem E, et al. Eur J Cancer Suppl 2007;5:241 (Abstract P#3020)
2Grothey A, et al. J Clin Oncol 2007;25(Suppl. 18):172s (Abstract 4036)
Bevacizumab adds clinical benefit when
combined with chemotherapy: BEAT and BRiTE
BEAT
BRiTE
10.9
n=1,914
Overall
10.1
n=1,953
11.6
n=503
FOLFIRI
10.9
n=280
11.2
n=552
FOLFOX
10.0
n=1,092
11.0
n=346
CAPOX
11.2
n=94
0
2.5
5.0
7.5
PFS (months)
10.0
Berry S, Van Cutsem E, et al. Presented at ASCO GI 2008 (Abstract 350)
Kozloff M, et al. Presented at ASCO GI 2007 (Abstract 375)
BRiTE and BEAT: serious AEs
of special interest to bevacizumab
B R iT E 1
n = 1 ,9 5 3 (% )
E ve n t
F irs t B E A T 2
n = 1 ,9 1 4 (% )
H yp e rte n s io n
1 9 .4
4 .8
G I p e rfo ra tio n
1 .8
1 .9
B le e d in g o r w o u n d -h e a lin g
c o m p lic a tio n
NR
1 .0
ATE
1 .8
1 .1
B le e d in g e v e n t
2 .4 *
2 .8
*Grade 3/4
 No new safety concerns for bevacizumab therapy
have been identified
1Grothey
NR = no response
A, et al. J Clin Oncol 2007;25(Suppl. 18):172s (Abstract 4036)
A, Van Cutsem E, et al. J Clin Oncol 2007;25(Suppl. 18):
181s (Abstract 4072)
2Kretzschmar
BRiTE: bevacizumab increases survival
post first progression
Post-progression therapy:
Bevacizumab post PD (n=642)
No bevacizumab post PD (n=531)
No treatment (n=253)
1.0
OS estimate
0.8
0.6
0.4
Post-progression
bevacizumab
HR=0.48 (0.41–0.57)
p<0.001
0.2
12.6
0
0
5
10
19.9
15
20
Months
31.8
25
30
35
Grothey A, et al. J Clin Oncol 2007;25(Suppl. 18):172s (Abstract 4036)
Withdrawal of anti-VEGF therapy
results in vessel regrowth
CD31
Untreated
AG-013736, 7 days
Withdrawal, 2 d
Withdrawal, 7 d
RIP-Tag2
Continue anti-angiogenic therapy to avoid vessel regrowth
VEGF = vascular endothelial growth factor
Mancuso MR, et al. J Clin Invest
2006;116:2610–21
Bevacizumab in the
neoadjuvant setting
Potential use of neoadjuvant
bevacizumab
Bevacizumab improves outcomes and has potential to
increase metastasectomy rates
Studies including
selected patients
(liver metastases only,
no extrahepatic disease)
(r=0.96, p=0.002)
0.6
Resection rate
0.5
0.4
Studies including all
patients with mCRC
(solid line)
(r=0.74, p<0.001)
0.3
0.2
Phase III studies
including all patients in
mCRC (dashed line)
(r=0.67, p=0.024)
0.1
0
0.3
0.4
0.5
0.6
0.7
Response rate
0.8
0.9
Folprecht G, et al. Ann Oncol 2005;16:1311–9
Potential use of neoadjuvant
bevacizumab (cont’d)
 Impaired wound healing and liver regeneration have
been associated with anti-VEGF therapies
 Using bevacizumab in patients who may become
eligible for surgery raises the question of
scheduling/best practice
Bevacizumab in mCRC patients undergoing
metastasectomy: retrospective analysis
Retrospective analysis of 1,186 patients with mCRC
Post operative
complication, n (%)
Any
Hepatobiliary
Wound
Chemotherapy
(n=44)
Bevacizumab +
chemotherapy
(n=81)
p value
19 (43)
40 (49)
0.51
5 (11)
4 (5)
0.20
11 (25)
23 (28)
0.68
Bevacizumab does not increase the risk of postoperative complications in
patients undergoing metastasectomy with curative intent
Kesmodel SV, et al. Presented at
ASCO GI 2007 (Abstract 234)
BEAT: surgery with curative intent
Overall population: rates of potentially
curative hepatic metastectomy
10
9.6
Patients with liver metastases only: rates of
potentially curative hepatic metastectomy
20.3
20
Hepatic metastectomy*
Hepatic metastectomy with
no residual disease (R0)**
7.3
15
6.2
5.6
5.3
5
Patients (%)
Patients (%)
7.0
15.4
15.2
14.3
12.1
11.7
10
0
n=27
n=33
n=54
n=71
n=85
n=107
n=34
n=43
n=76
n=99
n=114
n=145
5
0
Bevacizumab Bevacizumab Bevacizumab
+ chemo.
+ chemo.
+ chemo.
(all)
including
including
oxaliplatin
irinotecan
(n=1,914)
(n=946)
(n=662)
*Secondary endpoint; **Prospectively assessed
Updated data will be presented at the meeting
Bevacizumab Bevacizumab Bevacizumab
+ chemo.
+ chemo.
+ chemo.
(all)
including
including
oxaliplatin
irinotecan
(n=704)
(n=349)
(n=230)
Berry S, Van Cutsem E, et al. Eur J Cancer Suppl.
2007;5:241 (Abstract P#3020)
NO16966: surgery with curative intent
CAPOX/FOLFOX4 + placebo
CAPOX/FOLFOX4 + bevacizumab
ITT population
Patients with liver metastases only
10
19.2
20
8.4
6.1
Patients (%)
Patients (%)
15
5
12.9
10
5
0
0
Placebo
(n=701)
Bevacizumab
(n=699)
Placebo
(n=178)
Bevacizumab
(n=177)
Saltz L, et al. Proc World Congress on Gastrointestinal Cancer
2007 (Abstract O-0032)
Neoadjuvant bevacizumab in patients with
CRC: single-centre, non-randomised trial –
postoperative liver function and regeneration
Initial resection site
Full transverse image
Postoperative liver function and regeneration, assessed 3 months after
surgery by chemotherapy, normal in all but one patient
Gruenberger T, et al. Ann Oncol 2006;17(Suppl. 9)ix128 (Abstract 374P)
Gruenberger T, et al. Eur J Cancer Supp. 2007;5:255 (Abstract P#3064)
Surgery with curative intent in patients
receiving bevacizumab is feasible
 With appropriate management, bevacizumab can be used
in combination with chemotherapy with minimal risk of
bleeding/wound-healing complications in patients with
mCRC undergoing resection of metastases
 Data suggest that bevacizumab can be administered until
5 weeks prior to liver resection without any wound healing/
bleeding complications
 Liver generation following resection does not appear to be
affected in patients receiving bevacizumab in combination
with chemotherapy
EORTC GI Group Guidelines
FOLFOX/
CAPOX +
bevacizumab*
mCRC
FOLFIRI
Irinotecan +
cetuximab
Irinotecan +
cetuximab
FOLFOX/
CAPOX
FOLFOX/
CAPOX
Irinotecan +
cetuximab
FOLFOX/
CAPOX
FOLFIRI
FOLFIRI +
bevacizumab*
Capecitabine
(5-FU/LV) ±
bevacizumab*
*If no cardiovascular contraindications
EORTC = European Organisation for Research and Treatment of Cancer
Key bevacizumab trials in mCRC
Study
AVIRI1
NO169662
Treatment Bevacizumab + Bevacizumab +
regimen
FOLFIRI
FOLFOX-4/
CAPOX
Phase
Line of
therapy
IV
First line
III
First line
Status
Median PFS
(ECCO 2007)
Primary
endpoint met
(ASCO 2007)
1Sobrero
BEAT3
BRiTE4
Bevacizumab +
various chemotherapy
IV
First line
IV
First line
Efficacy
Efficacy update
update
(ASCO 2007)
(ECCO 2007)
A, et al. Eur J Cancer Suppl 2007;5:254 (Abstract P#3060)
L, et al. J Clin Oncol 2007;25(Suppl. 18):170s (Abstract 4028)
3Berry S, Van Cutsem E, et al. Eur J Cancer Suppl 2007;5:241 (Abstract P#3020)
4Grothey A, et al. J Clin Oncol 2007;25(Suppl. 18):172s (Abstract 4036)
2Saltz
Key capecitabine trials in mCRC
Study
Treatment
regimen
Phase
Line of
therapy
Status
NO169661
Bevacizumab +
FOLFOX-4/
CAPOX
NO169672
CAPOX vs
FOLFOX
ML169873
CAPOX vs
FOLFOX6
COFFE4
OXCAP vs
OXAFAFU
III
III
III
II/III
First line
Second line
First line
First line
Non-inferiority
of XELOX
shown
(ASCO 2007)
Equivalent RR
and PFS
(ECCO 2007)
Primary endpoint
Primary
met
endpoint met
(ASCO 2007)
(ECCO 2007)
1 Saltz
L, et al. J Clin Oncol 2007;25(Suppl. 18):170s (Abstract 4028)
ML, et al.J Clin Oncol 2007;25(Suppl. 18):171s (Abstract 4031)
3Ducreux M, et al. J Clin Oncol 2007;25(Suppl. 18):170s (Abstract 4029)
4Comella P, et al. Eur J Cancer Suppl 5:248 (Abstract P#3044)
2Rothenberg
Conclusions
 Bevacizumab combined with standard therapies is an
effective first-line treatment strategy for mCRC
 Bevacizumab is generally well tolerated
 Efficacy and safety outcomes in clinical evaluation
studies are similar to those reported in clinical trials
 Capecitabine is effectively replacing 5-FU in mCRC
 Data suggest that metastasectomy is feasible in
patients with mCRC treated with bevacizumab
plus chemotherapy