Forging a new standard in metastatic CRC

Eric Van CutsemUniversity Hospital Gasthuisberg

Leuven, Belgium

Advances in the treatment of mCRC

Median OS

35

30

25

20

15

10

5

0

Mo

nth

s

1980 1985 1990 1995 2000 2005+

5-FUBest supportive care

1980 1985 1990 1995 2000 2005 2010

IrinotecanCapecitabine

Oxaliplatin

Bevacizumaband EGFR inhibitors

mCRC = metastatic colorectal cancer; 5-FU = 5-fluorouracil; MoAbs = monoclonal antibodies; OS = overall survival

Capecitabine combinations are effective in the metastatic setting

CAPOXfirst line(n=80)

CAPIRIsecond line

(n=34)

CAPIRIfirst line(n=77)

CAPOXsecond line

(n=31)

ORR (%) 51 21 41 13

PFS (months) 6.2 5.2 7.1 4.3

OS (months) 16.512.9–18.5

18.815.7–23.7

Grothey A, et al. J Clin Oncol 2004;22:254 (Abstract 3534)

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 ratePFS = progression-free survivalb.i.d. = twice daily

Efficacy of capecitabine versus 5-FU/LV:meta-analysis of survival in six clinical trials

5-FU-based regimens(n=3,074)

Capecitabine-based regimens(n=3,097)

Median OS, months 22.5 23.1

(95% CI) (21.3–23.5) (22.1–24.4)

Hazard ratio (HR) 0.96

(95% CI) 0.90–1.02

Capecitabine is therapeutically noninferior to 5-FU/LVin 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

IFL

FOLFOX

FOLFIRI

FOLFOX/FOLFIRI

0 5 10 15 20 25 30

PFS

OS+ bevacizumab

+ bevacizumab

+ bevacizumab

+ bevacizumab

+ bevacizumab

MonthsLV = leucovorin; IFL = irinotecan, 5-FU, leucovorin; FOLFOX = leucovorin, 5-FU, oxaliplatinFOLFIRI = leucovorin, 5-FU, irinotecan

EARLY EFFECTS CONTINUED EFFECTS

1 Regression Normalisation2 Inhibition3

Linking the mechanism of action of bevacizumab with clinical benefit in mCRC

Decrease tumour size

Improve delivery of chemotherapy

Suppress new vessel growth

Enable metastasectomy

Increase PFS

Increase OS

Suppress regrowth via vessel ‘scaffolds’

Irinotecan-containing regimens with bevacizumab

and/or capecitabine

Hurwitz H, et al. N Engl J Med 2004;350:2335–42

AVF2107g: bevacizumab plus first-line IFL: superior PFS plus OS

6.2 10.6

IFL + bevacizumab

IFL + placebo

15.6 20.3

0 10 20 30 400 10 20 30

Median OS 15.6 vs 20.3 monthsHR=0.66 (p<0.001)

Median PFS6.2 vs 10.6 monthsHR=0.54 (p<0.0001)

IFL + bevacizumab

IFL + placebo

Months

1.0

0.8

0.6

0.4

0.2

0

Months

1.0

0.8

0.6

0.4

0.2

0

OS

est

imat

e

PF

S e

stim

ate

Bevacizumab plus FOLFIRI has been evaluated in several phase II trials

Study 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

1Fuchs CS, et al. J Clin Oncol 2007;25:4779–862Samelis GF, et al. ASCO GI Cancers Symposium 2007 (Abstract 394)

3Kopetz S, et al. ASCO GI Cancers Symposium 2007 (Abstract 4089)mIFL = irinotecan, 5-FU, leucovorin

Phase IV trial of bevacizumab plus FOLFIRI (AVIRI): study design

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

Patients with previously untreated, unresectable

mCRC(n=209)

Patients with previously untreated, unresectable

mCRC(n=209)

Bevacizumab + FOLFIRIBevacizumab + FOLFIRI

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) (%) 7.7

Disease control rate (%) 85.6

Median PFS and OS is comparable to that observed with bevacizumab plus IFL in the pivotal AVF2107g trial

Ackland S, et al. Presented at ASCO GI 2008 (Abstract 463)ITT = intent to treat

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 FOLFIRIis consistent with that reported for bevacizumab

plus other standard chemotherapy regimens

Ackland S, et al. Presented at ASCO GI 2008 (Abstract 463)

FOLFIRI(n=144)

Initial design

n=430

Bevacizumab + mIFL (n=57)

n=117

Primary endpoint: PFS

BICC-C: bevacizumab plus irinotecan-based chemotherapy

Protocol amended due to approval of bevacizumab

Amended design

mIFL(n=141)

CAPIRI(n=145)

RR

Bevacizumab + FOLFIRI (n=60)

Fuchs CS, et al. J Clin Oncol 2007;25:4779–86

Before protocol amendment

Regimen

After protocol amendment

Bevacizumab +

Efficacy FOLFIRI mIFL CAPIRI FOLFIRI mIFL

Median PFS (months) 7.6 5.9 5.8 11.2 8.3

Median OS (months) 23.1 17.6 18.9 28 19.2

ORR (%) 47 43 39 58 53

BICC-C: bevacizumab plus irinotecan-based chemotherapy – efficacy

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;25:4779–86Fuchs CS, et al. J Clin Oncol 2007;26:689–90

Bevacizumab plus FOLFIRI in first-line mCRC: impact on PFS

BICC-C

Kopetz

AVIRI

BRiTE

BEAT

Tournigand

Months

FOLFIRI

FOLFIRI + bevacizumab

FOLFIRI + bevacizumab

FOLFIRI + bevacizumab

FOLFIRI + bevacizumab

FOLFIRI + bevacizumab

n=109

n=504

n=280

n=209

n=41

n=57

Tournigand C, et al. J Clin Oncol 2004;22:229–37Berry 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

0 2.5 5.0 7.5 10.0 12.5 15.0

Oxaliplatin-containing regimens with bevacizumab

and/or capecitabine

7.34.7

Giantonio BJ, et al. J Clin Oncol 2007;25:1539–44

E3200: bevacizumab second line: superior PFS plus OS with FOLFOX4

FOLFOX4 + bevacizumab

FOLFOX4

FOLFOX4 + bevacizumab

FOLFOX4

12.910.8

Median PFS 4.7 vs 7.3 monthsHR=0.61 (p<0.0001)

Median OS10.8 vs 12.9 monthsHR=0.75 (p=0.0011)

Months

1.0

0.8

0.6

0.4

0.2

0

Months

1.0

0.8

0.6

0.4

0.2

0

OS

est

imat

e

0 3 6 9 12 15 18 21 24 27 30 33 36

PF

S e

stim

ate

0 2 4 6 8 10 12 14 16 18 20 22 24 26

CAPOX is equivalent to FOLFOXin phase II/III studies

n CAPOX FOLFOX CAPOX FOLFOXCAPO

XFOLFOX

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

NO169676 627 20.1 17.5 4.7 4.8 11.9 12.6

SICOG04017 322 34 33 6.4 6.2 — —

1Porschen 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)

OS (months)PFS (months)ORR (%)

Previously untreated mCRC (n=255)

PD or toxicity

Phase II trial of first-line bevacizumab plus CAPIRI or CAPOX (AIO): study design

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 or toxicity

Schmiegel WH, et al. J Clin Oncol 2007;25(Suppl. 18):172s (Abstract 4034)

CAPOX + bevacizumab 7.5mg/kg every 3 weeks

CAPIRI + bevacizumab 7.5mg/kg every 3 weeks

PD = progressive disease

Phase II trial of first-line bevacizumab plus CAPIRI or CAPOX (AIO): efficacy

Outcome (%)

Bevacizumab + CAPOX (n=118)

Bevacizumab + CAPIRI (n=112)

ORR CR PR

45 540

47 443

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

Grade 3/4 AE (%)Bevacizumab + CAPOX (n=117)

Bevacizumab + CAPIRI (n=112)

Diarrhoea 16 13

Sensory neuropathy 13 0

Hand-foot syndrome 6 4

Vomiting 3 4

Fever 1 0

Neutropenia 2 4

Thrombocytopenia 4 0

Fatigue 2 2

Ileus 2 1

Alopecia 0 1

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

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)

Initial two-arm open-label study

(n=1,000)

CAPOX +placebo (n=350)

FOLFOX4 +placebo (n=351)

CAPOX + bevacizumab

(n=350)

FOLFOX4 + bevacizumab

(n=349)

CAPOX (n=317)

FOLFOX4 (n=317)

Protocol amended to 2 x 2 placebo-controlled design after bevacizumab phase III data became

available (n=1,400)

RecruitmentJune 2003 – May 2004

RecruitmentFebruary 2004 – February 2005

NO16966: PFS – chemotherapy plus bevacizumab (general and on-treatment

populations)

FOLFOX4 or CAPOX + placebo

FOLFOX4 or CAPOX + bevacizumab

Bevacizumab-containing arm: separation occurs between the PFS for general versus on-treatment populations after 6 months (vertical arrow)

On treatment: HR=0.63 (97.5% CI: 0.52–0.75)

p<0.0001

0 5 10 15 20

1.0

0.8

0.6

0.4

0.2

0

PF

S e

stim

ate

PFS (months)

General: HR=0.83 (97.5% CI: 0.72–0.95)

p=0.0023

Saltz L, et al. J Clin Oncol 2007;25(Suppl. 18):170s (Abstract 4028)

CAPOX/FOLFOX4 + bevacizumab

CAPOX/FOLFOX4 + placebo

21.219.9

Median OS 19.9 vs 21.2 monthsHR=0.89 (p=0.0769)

9.48.0

Median PFS8.0 vs 9.4 monthsHR=0.83 (p=0.023)

Saltz L, et al. Proc World Congress on Gastrointestinal Cancer 2007 (Abstract O-0032)

NO16966: bevacizumab first-line – PFS plus OS with CAPOX/FOLFOX4

Months

1.0

0.8

0.6

0.4

0.2

0

Months

1.0

0.8

0.6

0.4

0.2

0

OS

est

imat

e

0 6 12 18 24 30 360 5 10 15 20 25

PF

S e

stim

ate

CAPOX/FOLFOX4 + bevacizumab

CAPOX/FOLFOX4 + placebo

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 toleratedwhen combined with oxaliplatin- or

capecitabine-based regimens

Saltz L, et al. J Clin Oncol 2007;25 (Suppl. 18):170s (Abstract 4028)

Grade 3/4 AE

FOLFOX4/CAPOX + placebo

n=675 (%)

FOLFOX4/CAPOX + bevacizumab

n=694 (%)

Any grade 3/4 AE 75 80

GI perforations <1 <1

Bleeding 1 2

ATE 1 2

Hypertension 1 4

Proteinuria – <1

Wound-healing complication <1 <1

Discontinuations due to an adverse event

21

31

All-cause 60-day mortality 1.6 2

Treatment-related mortality up to 28 days after last dose

1.5

2

Bevacizumab in the clinical setting

Data from BEAT and BRiTE

Bevacizumab plus first-line chemotherapy in clinical practice: BEAT and BRiTE

Bevacizumab + chemotherapy

PD

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)

PD

BRiTE2

BEAT1

Patients with previously untreated, unresectable

mCRC (n=1,953)

Bevacizumab + chemotherapy

Patients with previously untreated, unresectable

mCRC (n=1,914)

11.2

10.9

11.0

11.2

11.6

10.9

10.1

10.0

CAPOX

FOLFOX

FOLFIRI

Overall

PFS (months)

Bevacizumab adds clinical benefit when combined with chemotherapy: BEAT and BRiTE

n=1,914

n=503

n=552

n=346

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)

n=1,953

n=280

n=1,092

n=94

0 2.5 5.0 7.5 10.0

BEAT BRiTE

BRiTE and BEAT: serious AEs of special interest to bevacizumab

1Grothey A, et al. J Clin Oncol 2007;25(Suppl. 18):172s (Abstract 4036)2Kretzschmar A, Van Cutsem E, et al. J Clin Oncol 2007;25(Suppl. 18):

181s (Abstract 4072)

*Grade 3/4

Event

BRiTE1 n=1,953 (%)

First BEAT2 n=1,914 (%)

Hypertension 19.4 4.8

GI perforation 1.8 1.9

Bleeding or wound-healing complication

NR

1.0

ATE 1.8 1.1

Bleeding event 2.4* 2.8

No new safety concerns for bevacizumab therapyhave been identified

NR = no response

1.0

0.8

0.6

0.4

0.2

0 0 5 10 15 20 25 30 35

Months

OS

est

imat

e

Bevacizumab post PD (n=642)No bevacizumab post PD (n=531)No treatment (n=253)

Post-progression therapy:

12.6 19.9 31.8

Grothey A, et al. J Clin Oncol 2007;25(Suppl. 18):172s (Abstract 4036)

BRiTE: bevacizumab increases survival post first progression

Post-progressionbevacizumabHR=0.48 (0.41–0.57)p<0.001

Withdrawal of anti-VEGF therapyresults in vessel regrowth

Continue anti-angiogenic therapy to avoid vessel regrowth

Mancuso MR, et al. J Clin Invest 2006;116:2610–21

CD31 Untreated AG-013736, 7 days Withdrawal, 2 d Withdrawal, 7 d

RIP-Tag2

VEGF = vascular endothelial growth factor

Bevacizumab in the neoadjuvant setting

Phase III studies including all patients in mCRC (dashed line)(r=0.67, p=0.024)

Potential use of neoadjuvant bevacizumab

Studies including all patients with mCRC (solid line) (r=0.74, p<0.001)

Studies includingselected patients(liver metastases only, no extrahepatic disease)(r=0.96, p=0.002)

Res

ecti

on

rat

e

Response rate

0.6

0.5

0.4

0.3

0.2

0.1

00.3 0.4 0.5 0.6 0.7 0.8 0.9

Bevacizumab improves outcomes and has potential to increase metastasectomy rates

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

Kesmodel SV, et al. Presented at ASCO GI 2007 (Abstract 234)

Post operative complication, n (%)

Chemotherapy (n=44)

Bevacizumab + chemotherapy

(n=81) p value

Any 19 (43) 40 (49) 0.51

Hepatobiliary 5 (11) 4 (5) 0.20

Wound 11 (25) 23 (28) 0.68

Bevacizumab does not increase the risk of postoperative complications in patients undergoing metastasectomy with curative intent

BEAT: surgery with curative intentP

atie

nts

(%

)

n=

145

n=

114

n=

99

n=

76

n=

43

n=

34

Bevacizumab + chemo.

(all)

Bevacizumab + chemo. including oxaliplatin

Bevacizumab + chemo. including irinotecan(n=1,914)

(n=946) (n=662)

10

5

0

7.0

9.6

6.25.6

7.3

5.3

20

15

10

5

0

Pat

ien

ts (

%)

Bevacizumab + chemo.

(all)

Bevacizumab + chemo. including oxaliplatin

Bevacizumab + chemo. including irinotecan(n=704)

(n=349) (n=230)

n=

107

n=

85

n=

71

n=

54

n=

33

n=

27

15.214.3

12.1

15.4

11.7

*Secondary endpoint; **Prospectively assessedUpdated data will be presented at the meeting

Overall population: rates of potentiallycurative hepatic metastectomy

Patients with liver metastases only: rates of potentially curative hepatic metastectomy

Hepatic metastectomy withno residual disease (R0)**

Hepatic metastectomy*

Berry S, Van Cutsem E, et al. Eur J Cancer Suppl. 2007;5:241 (Abstract P#3020)

20.3

NO16966: surgery with curative intentP

atie

nts

(%

) 6.1

8.4

12.9

19.210

5

0

20

15

10

5

0

Pat

ien

ts (

%)

Placebo Bevacizumab(n=701) (n=699)

Placebo Bevacizumab(n=178) (n=177)

ITT population Patients with liver metastases only

CAPOX/FOLFOX4 + bevacizumabCAPOX/FOLFOX4 + placebo

Saltz L, et al. Proc World Congress on Gastrointestinal Cancer 2007 (Abstract O-0032)

Initial resection site Full transverse image

Postoperative liver function and regeneration, assessed 3 months after surgery by chemotherapy, normal in all but one patient

Neoadjuvant bevacizumab in patients with CRC: single-centre, non-randomised trial –

postoperative liver function and regeneration

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 usedin 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 until5 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

Irinotecan + cetuximab

Irinotecan + cetuximab

FOLFIRIFOLFOX/CAPOX +

bevacizumab*

Irinotecan + cetuximab

FOLFOX/CAPOX

FOLFIRI + bevacizumab*

FOLFIRIFOLFOX/CAPOX

Capecitabine (5-FU/LV) ±

bevacizumab*

*If no cardiovascular contraindicationsEORTC = European Organisation for Research and Treatment of Cancer

mCRC

Key bevacizumab trials in mCRC

1Sobrero A, et al. Eur J Cancer Suppl 2007;5:254 (Abstract P#3060) 2Saltz 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)

Study AVIRI1 NO169662 BEAT3 BRiTE4

Treatment regimen

Bevacizumab +FOLFIRI

Bevacizumab + FOLFOX-4/

CAPOX

Bevacizumab + various chemotherapy

Phase IV III IV IVLine of therapy

First line First line First line First line

Status Median PFS (ECCO 2007)

Primary endpoint met(ASCO 2007)

Efficacy update

(ECCO 2007)

Efficacy update(ASCO 2007)

Key capecitabine trials in mCRC

1 Saltz L, et al. J Clin Oncol 2007;25(Suppl. 18):170s (Abstract 4028) 2Rothenberg 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)

Study NO169661 NO169672 ML169873 COFFE4

Treatment regimen

Bevacizumab + FOLFOX-4/

CAPOX

CAPOX vs FOLFOX

CAPOX vs FOLFOX6

OXCAP vs OXAFAFU

Phase III III III II/III

Line of therapy First line Second line First line First line

Status Primary endpoint met

(ASCO 2007)

Primary endpoint met (ECCO 2007)

Non-inferiority of XELOX

shown (ASCO 2007)

Equivalent RR and PFS

(ECCO 2007)

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