Avastin ® : setting the standard in treatment for metastatic colorectal cancer (CRC) Fairooz Kabbinavar David Geffen School of Medicine at UCLA Los Angeles,

Avastin®: setting the standard in treatment for metastatic colorectal

cancer (CRC) Fairooz Kabbinavar

David Geffen School of Medicine at UCLALos Angeles, USA

Treating cancer with Avastin

Avastin has positive survival data in large trials in metastatic CRC, in combination with

• irinotecan-based regimens in first line1

• oxaliplatin-based regimens in second line2

• 5-FU/LV in first line3

1Hurwitz H, et al. N Engl J Med 2004;350:2335–422Giantonio BJ, et al. J Clin Oncol 2005;23(June 1 Suppl.):1s

(Abstract 2)3Kabbinavar FF, et al. J Clin Oncol 2005;23:3706–12

CRC = colorectal cancer5-FU = 5-fluorouracilLV = leucovorin

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

Phase III trial of IFL ± Avastin (AVF2107g): study design

May receive Avastin beyond

disease progression

No Avastin beyond disease

progression

May receive Avastin beyond

disease progression

Previously untreated

metastatic CRC(n=923)

IFL* + placebo(n=411)

IFL* + Avastin (5mg/kg, every

2 weeks)(n=402)

5-FU/LV† + Avastin (5mg/kg, every

2 weeks)(n=110)

Arm closed to enrolment

Primary endpoint: duration of survival

IFL = irinotecan, 5-FU/LV*Bolus 5-FU/LV†Roswell Park regimen

Phase III trial of IFL ± Avastin (AVF2107g): progression-free

survival

Median progression-free survivalIFL + placebo: 6.2 (95% CI: 5.6–7.7)IFL + Avastin: 10.6 (95% CI: 9.0–11.0) HR=0.54 (95% CI: 0.45–0.66) p<0.001

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1.0

0.8

0.6

0.4

0.2

00 10 20 30

Progression-free survival (months)

6.2 10.6

IFL + Avastin

IFL + placebo


Phase III trial of IFL ± Avastin (AVF2107g): survival

Median survivalIFL + placebo: 15.6 (95% CI: 14.3–17.0) vsIFL + Avastin: 20.3 (95% CI: 18.5–24.2)HR=0.66 (95% CI: 0.54–0.81)p<0.001

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1.0

0.8

0.6

0.4

0.2

00 10 20 30 40

Survival (months)

IFL + Avastin

IFL + placebo

15.6 20.3


Treatment schema for metastatic CRC

First line FOLFOX(XELOX)

Avastin +

IFL5-FU/LV(Xeloda)

IFL = irinotecan, 5-FU/LV FOLFOX = 5-FU/LV + oxaliplatinXELOX = Xeloda + oxaliplatin

Combined analysis of Avastin plus 5-FU-based regimens: methodology

Analysis of results from phase II and III studies of IFL or 5-FU/LV ± Avastin in metastatic CRC (trials AVF2107, AVF0780 and AVF2192)

• combined control group: those randomised to 5-FU/LV or IFL

• comparator arm: patients randomised to 5-FU/LV plus Avastin 5mg/kg every 2 weeks

Kabbinavar FF, et al. J Clin Oncol 2005;23:3706–12

Combined analysis of Avastin plus 5-FU-based regimens: overall

survivalSurv

ival (%

)

100

80

60

40

20

00 10 20 30 40

Months since treatment initiation

Median survival: 14.6 vs 17.9 monthsHR=0.74, p=0.0081

5-FU/LV/Avastin 5mg/kg

5-FU/LV or IFL

14.6 17.9


Combined analysis of Avastin plus 5-FU-based regimens: progression-free

survivalPro

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n-f

ree s

urv

ival (%

)

100

80

60

40

20

00 10 20 30

Months since treatment initiation

Median progression-free survival: 5.6 vs 8.8 monthsHR=0.63, p=0.0001

5-FU/LV/Avastin 5mg/kg

5-FU/LV or IFL

5.6 8.8



First line FOLFOX(XELOX)

Avastin +

IFL

Avastin +

5-FU/LV(Xeloda)

Avastin plus FOLFOX in second line metastatic CRC (E3200): study

design

FOLFOX4 + Avastin(10mg/kg, every

2 weeks)(n=289)

FOLFOX4(n=290)

Avastin (10mg/kg, every 2 weeks)

(n=243)

Metastatic CRC patients previously

treated with an irinotecan-based

regimen(n=822)

PD

PD

PD

Giantonio BJ, et al. J Clin Oncol 2005;23(June 1 Suppl.):1s (Abstract

2)PD = progression of disease

Primary endpoint: duration of survival

E3200: overall survivalPro

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Time (months)AliveDead MedianTotal

A: FOLFOX4 + Avastin 289 246 43 12.9B: FOLFOX4 290 257 33 10.8C: Avastin 243 216 27 10.2

HR=0.76A vs B: p=0.0018B vs C: p=0.95

HR = hazard ratio Giantonio BJ, et al. J Clin Oncol 2005;23(June 1 Suppl.):1s (Abstract 2)

10.2 12.9

10.8

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

A: FOLFOX4 + Avastin

C: Avastin B: FOLFOX4

First-line trial with various oxaliplatin-based regimens (TREE-2): study design

First-line metastatic CRC (n=223)

mFOLFOX6 + Avastin5mg/kg every 2 weeks

(n=75)

XELOX + Avastin7.5mg/kg every 3

weeks (n=74)

bFOL + Avastin 5mg/kg every 2 weeks

(n=74)

PD

PD

PD

Primary endpoint: grade 3/4 toxicitySecondary endpoints include overall response rate, time to progression and overall survival

Hochster HS, et al. Presented at: 2006 Gastrointestinal Cancers Symposium; 26–28 January 2006; San Francisco, Ca. Abstract 244

TREE-2: overall response rate

0

10

20

30

40

50

60

Resp

on

se r

ate

(%

)

mFOLFOX6 + Avastin

bFOL + Avastin

XELOX + Avastin

52.1

34.3

45.8


TREE-2: time to tumour progressionPro

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0.8

0.6

0.4

0.2

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Time (months)

CapeOx + Avastin

FOLFOX + Avastin

bFOL + Avastin


TREE-2: time to treatment failurePro

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0.6

0.4

0.2

0

Time (months)

0 5 10 15 20


CapeOx + Avastin

FOLFOX + Avastin

bFOL + Avastin


First line

Avastin +

IFL

Avastin +

5-FU/LV(Xeloda)

Avastin +

FOLFOX(XELOX)

When to use Avastin?

Setting Combination partner Efficacy outcomes

First line IFL (vs IFL + placebo) Superior response rate, PFS, OS

5-FU/LV (vs 5-FU/LV) Superior response rate, PFS, OS*

Oxaliplatin-based (vs oxaliplatin-based therapy without Avastin)

Superior response rate

Second line FOLFOX (vs FOLFOX) Superior response rate, PFS, OS

Cetuximab plus irinotecan or cetuximab alone

Impressive response (in phase II trial) and PFS

1Hurwitz H, et al. N Engl J Med 2004;350:2335–42; 2Kabbinavar FF, et al. J Clin Oncol 2005;23:3706–12; 3Hurwitz HI, et al. J Clin Oncol 2005;23:3502–8; 4Hochster HS, et al. J Clin

Oncol 2005;23(June 1 Suppl.): (Abstract 3515); 5Giantonio BJ, et al. J Clin Oncol 2005;23(June 1 Suppl):1s (Abstract 2); 6Saltz L, et al. J Clin Oncol 2005;23 (June 1 Suppl.): (Abstract 3508);

7Chen H, et al. J Clin Oncol 2004;22 (July 15 Suppl.): (Abstract 3515)

*OS benefit observed with 5-FU/LV is a result of a combined analysis2

Why is Avastin not used in the second line?

Superior efficacy with Avastin when it is used early in disease progression• Immature vasculature is more reliant on VEGF for

survival

Despite the efficacy benefits observed in the second-line, first-line use of Avastin provides better patient outcomes• Avastin has suboptimal efficacy in terms of patient

survival and response rates in the second-line setting

Who to treat with Avastin

Subgroup analyses have shown that adding Avastin to IFL improves overall survival and progression-free survival independent of baseline patient risk factors, including

• age

• gender

• performance status

• location of primary tumour

• number of metastatic sites

• duration of metastatic disease

• biomarker status (k-ras, b-raf or p53 mutation status, P53 expression or VEGF expression)

Hurwitz H, et al. N Engl J Med 2004;350:2335–42Hurwitz H, et al. Presented at ASCO GI 2006

Koeppen H, et al. Eur J Cancer Suppl 2004;2:48 (Abstract 150)

How long should Avastin treatment be continued?

Avastin should be used until disease progression, the treatment strategy in all clinical trials of Avastin to date

The toxicity of oxaliplatin/irinotecan-based combinations often leads to regimen modification prior to progression

• it is important not to stop Avastin treatment in these patients

• Avastin plus 5-FU/LV appears to be as active as FOLFOX/FOLFIRI in this population, and therefore a suitable treatment strategy if toxicity leads to oxaliplatin/irinotecan withdrawal

• Avastin also has some activity as monotherapy

Do patients who do not respond derive benefit from Avastin therapy?

Due to the disparity between progression-free survival/overall survival and response in the IFL ± Avastin trial,1 Mass et al.2 performed an exploratory analysis to examine clinical outcome in patients who responded to treatment versus those who did not

Patients were grouped by best response achieved • complete/partial responses• stable/progressive disease or non-evaluable (designation of stable

disease required at least two post-baseline tumour assessments as per RECIST)

Results of this exploratory analysis provide further rationale for treatment until progression with Avastin

1Hurwitz H, et al. N Engl J Med 2004;350:2335–422Mass RD, et al. J Clin Oncol 2005;23(June 1 Suppl.):249s (Abstract

3514)

RECIST = Response Evaluation Criteria in Solid Tumours

Clinical benefit of Avastin in responding and non-responding patients with metastatic CRC: overall

survival

Mass RD, et al. J Clin Oncol 2005;23(June 1 Suppl.):249s (Abstract 3514)

1.0

0.8

0.6

0.4

0.2

00 10 20 30 40

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Time (months)

IFL/Avastin (responders, n=180)IFL/placebo (responders, n=143)IFL/Avastin (non-responders, n=222)IFL/placebo (non-responders, n=268)

IFL/Avastin (non-responders, n=222)IFL/placebo (non-responders, n=268)

Clinical benefit of Avastin in responding and non-responding patients with metastatic CRC:

progression-free survival

1.0

0.8

0.6

0.4

0.2

00 10 20 30

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Time (months)

IFL/Avastin (responders, n=180)IFL/placebo (responders, n=143)

Mass RD, et al. J Clin Oncol 2005;23(June 1 Suppl.):249s (Abstract 3514)

Safety profile of Avastin

Effect of adding Avastin to chemotherapy

Avastin does not significantly increase the incidence of chemotherapy-related adverse events such as diarrhoea and leucopenia1–3

The addition of Avastin to chemotherapy1 did not increase significantly the incidence of adverse events leading to

• death within 60-days

• death

• hospitalisation

• discontinuation

1Hurwitz H, et al. N Engl J Med 2004;350:2235–422Kabbinavar F, et al. J Clin Oncol 2003;21:60–5

3Kabbinavar FF, et al. J Clin Oncol 2005;23:3697–7054Roche. Data on file

Avastin-related events in CRC trials to date: overview

Phase II/III CRC trials have identified a number of side effects associated with Avastin therapy

Many side effects are mild to moderate in severity and manageable using standard therapies, including• hypertension (most common)• proteinuria• bleeding

Relatively uncommon adverse events associated with Avastin therapy include• arterial thrombosis• effects on wound healing• GI perforation

Kabbinavar F, et al. J Clin Oncol 2003;21:60–5Hurwitz H, et al. N Engl J Med 2004;350:2335–42

Giantonio BJ, et al. J Clin Oncol 2005;23(June 1 Suppl.):1s (Abstract 2)


Hypertension: incidence

Trial

Regimen

All grades

Grade 3/4

Grade 3

Grade 4

E32001 FOLFOX – – 2 <1

FOLFOX + Avastin (10mg/kg) – – 5 1

Avastin (10mg/kg) – – 7 0

AVF0780g2 5-FU/LV 3 0 – –

5-FU/LV + Avastin (5mg/kg) 11 8.6 – –

5-FU/LV + Avastin (10mg/kg) 28 25 – –

AVF2107g3 IFL 8.3 – 2.3 0

IFL + Avastin (5mg/kg) 22.4 – 11 0

AVF2192g4 5-FU/LV 5 – 3 0

5-FU/LV + Avastin (5mg/kg) 32 – 16 0

1Giantonio BJ, et al. J Clin Oncol 2005:23(June 1 Suppl.):1s (Abstract 2)2Kabbinavar F, et al. J Clin Oncol 2003;21:60–5

3Hurwitz H, et al. N Engl J Med 2004;350:2235–424Kabbinavar FF, et al. J Clin Oncol 2005;23:3697–705

Hypertension

An increased incidence of hypertension is observed in patients treated with Avastin

Effectively managed using oral antihypertensives• angiotensin-converting enzyme inhibitors

• calcium channel blockers

Hypertensive crisis is rare but requires discontinuation of treatment

Recommendations• blood pressure monitored while on therapy

• in patients with severe hypertension requiring medical therapy, Avastin therapy should be temporarily interrupted until adequate control is achieved

• if hypertension cannot be controlled with medical therapy, Avastin should be permanently discontinued

Avastin Summary of Product Characteristics

ATEs*: results of a pooled analysis of five studies

Higher risk observed in patients with history of ATEs and aged ≥65 years, hypertension and proteinuria

*Pooled analysis of five randomised trialsATE = arterial thromboembolic event

Skillings JR, et al. J Clin Oncol 2005;23(June 1 Suppl.):196s (Abstract 3019)

†p=0.076; ‡p=0.03CI = confidence interval

Chemotherapy alone

(n=782)

Avastin + chemotherapy

(n=963)

ATEs, n (%) 13 (1.7) 37 (3.8)

Person-years of observation 419 673

Rate/100 person-years (95% CI) 3.1 (1.7–5.3) 5.5† (3.9–7.6)

Hazard ratio (95% CI) 1.99‡ (1.05–3.75)

Management of thromboembolic events

In the Hurwitz trial1 patients who were treated with full-dose anticoagulation for thrombotic events, while continuing study medication, showed no increase in the risk of haemorrhagic complications2

53 of 392 (14%) patients in the IFL plus Avastin arm had a thrombotic event treated with full-dose anticoagulation therapy (warfarin)2

• median time of treatment with full-dose warfarin on study for these patients was 218 days

1Hurwitz H, et al. N Engl J Med 2004;350:2335–422Hambleton J, et al. J Clin Oncol 2004;22(July 15 Suppl.): Abstract

3528

TherapyPatients receiving full

dose warfarin (n)

Grade 3/4 bleeding incidence

(%)

Avastin + IFL 53 2 (3.8)

Placebo + IFL 30 2 (6.7)

Thromboembolic events: summary

Adding Avastin to 5-FU-based chemotherapy does not increase the incidence of venous thromboembolism1

ATEs are increased, but remain relatively uncommon1

Patients with a history of ATEs or aged >65 years are at an increased risk of developing ATEs during therapy

• caution should be taken when treating these patients with Avastin2

Recommendation

• patients who develop ATEs should discontinue Avastin2

1Novotny WF, et al. J Clin Oncol 2004;22(July 15 Suppl.): Abstract 35292Avastin Summary of Product Characteristics

Wound healing/bleeding in metastatic CRC patients who undergo surgery prior to and during treatment

with Avastin

Wound healing/bleeding complications IFL + placebo IFL + Avastin

Surgery 28–60 days prior to therapy1 1/155 3/150

Surgery on therapy2 0/25 4/40

1Scappaticci F, et al. J Clin Oncol 2004;22(July 15 Suppl.): Abstract 35302Hurwitz H, et al. J Clin Oncol 2004;22(July 15 Suppl.): Abstract 3702

Wound healing

Avastin therapy may adversely affect the wound healing process

Major surgical procedures in CRC patients treated with Avastin may uncommonly lead to wound healing complications1,2

No evidence that Avastin increases the risk of complications in patients who have undergone surgery >28 days prior to Avastin therapy2

Avastin therapy should be discontinued3

• in patients who experience wound healing complications during therapy until the wound is fully healed

• for at least 28 days following major surgery or until the surgical wound is fully healed

• prior to elective surgery

1Hurwitz H, et al. J Clin Oncol 2004;22(July 15 Suppl.): Abstract 37022Scappaticci F, et al. J Clin Oncol 2004;22(July 15 Suppl.): Abstract

35303Avastin Summary of Product Characteristics

Bleeding: incidence

Trial Regimen All grades Grade 3/4 Grade 3 Grade 4

E32001 FOLFOX <1 0

FOLFOX + Avastin (10mg/kg) 2.8 <1

Avastin (10mg/kg) – – 2 0

AVF0780g2 5-FU/LV 11* 0*

5-FU/LV + Avastin (5mg/kg) 52* 0*

5-FU/LV + Avastin (10mg/kg) 69* 9.4*

AVF2107g3 IFL 2.5

IFL + Avastin (5mg/kg) 3.1

AVF2192g4 5-FU/LV 3

5-FU/LV + Avastin (5mg/kg) 5

*Epistaxis + GI haemorrhage

1Giantonio BJ, et al. J Clin Oncol 2005:23(June 1 Suppl.):1s (Abstract 2)2Kabbinavar F, et al. J Clin Oncol 2003;21:60–5; 3Hurwitz H, et al. N Engl J Med 2004;350:2235–

42 4Kabbinavar FF, et al. J Clin Oncol 2005;23:3697–705

Bleeding in patients taking aspirin at baseline

Chemotherapy alone Chemotherapy + Avastin

No aspirin Aspirin No aspirin Aspirin

Grade 1/2 bleeding, n (%)

57/216 (26.4)

6/21 (28.6)

177/341 (51.9)

18/37 (48.6)

Grade 3/4 bleeding, n (%)

12/495 (2.4)*

1/40 (2.5)

26/600 (4.3)*

2/68 (2.9)

Rate (grade 3/4)/ 100 person-years (95% CI)

4.16

(2.2–7.3)

3.95

(0.1–22.0)

5.6

(3.7–8.2)

3.57

(0.4–12.9) n=1,203 for grade 3/4 bleeding

n=615 for grade 1/2 bleeding

Hambleton J, et al. J Clin Oncol 2005;23(June 1 Suppl.):259s (Abstract 3554)

*Adjustment for time on therapy resulted in a numerically increased incidence of grade 3/4 bleeding with Avastin, but the difference was not statistically significant

Bleeding

Patients treated with Avastin may have an increased risk of developing tumour-associated haemorrhage

Epistaxis is the most common bleeding event associated with Avastin in patients with metastatic CRC• easily managed using standard first-aid techniques

Avastin is contraindicated in patients with untreated CNS metastases

Recommendations• Avastin should be permanently discontinued in patients who

experience grade 3 or 4 bleeding during therapy

Avastin Summary of Product CharacteristicsCNS = central nervous system

GI perforation

Trial Therapy n Incidence, n (%) Deaths, n (%)

AVF2192g1 5-FU/LV + Avastin 100 2 (2.0) 1 (1.0)

E22002 IFL + Avastin 86 2 (2.3) 1 (1.1)

E32003 FOLFOX4 + Avastin Avastin

287 234

3 (1.0) 3 (1.3)

– –

AVF2107g IFL + Avastin4 or 5-FU/LV + Avastin5

394 109

7 (1.4) 0

2 (0.4) 0

TREE-26 FOLFOX + Avastin or XELOX + Avastin or bFOL + Avastin

213 2 (2.8) 2 (2.8) 3 (4.2)

NR

GI perforation: incidence andmortality rate

1Kabbinavar FF, et al. J Clin Oncol 2005;23:3697–7052Giantonio BJ, et al. J Clin Oncol 2004;22(July 15 Suppl.): Abstract 30173Giantonio BJ, et al. J Clin Oncol 2005;23(June 1 Suppl.):1s (Abstract 2)

4Hurwitz H, et al. N Engl J Med 2004;350:2335–42 (Roche data on file)5Hurwitz HI, et al. J Clin Oncol 2005;23:3502–8

6Hochster HS, et al. J Clin Oncol 2005;23(June 1 Suppl.):249s (Abstract 3515)

NR = not reported;bFOL = bolus 5-FU/LV + oxaliplatin

GI perforation

Patients with metastatic carcinoma of the colon or rectum and an intra‑abdominal inflammatory process may be at increased risk of developing GI perforation when treated with Avastin and chemotherapy

Uncommon but life-threatening event• 1.4–2.0% of patients with metastatic CRC treated with Avastin1–4

• more than 50% of patients experiencing GI perforation have one or more identified potential risk factor5

Recommendations4

• caution should be exercised when treating patients with metastatic carcinoma of the colon or rectum

• Avastin therapy should be permanently discontinued in patients who develop GI perforation

1Kabbinavar FF, et al. J Clin Oncol 2005;23:3697–705; 2Giantonio BJ, et al. J Clin Oncol 2005;23(June 1 Suppl.):1s (Abstract 2); 3Hurwitz H, et al. N Engl J Med

2004;350:2235–42; 4Avastin Summary of Product Characteristics; 5Kozloff M, et al. Presented at: 2006 Gastrointestinal Cancers Symposium; 26–28 January 2006;

San Francisco, Ca. Abstract 247

BRiTE: US observation studyFirst-BEAT: Roche Expanded Access

Programme

Updated results

BRiTE: first-line chemotherapy regimens used on study

60

50

40

30

20

10

0

Pati

ents

(%

)

Infu

siona

l

5-FU

/LV

Bolus

5-F

U/LV

Capec

itabi

ne

FOLF

IRI

IFL

XELIR

I

IROX

FOLF

OXFL

OX

XELOX

Other

FOLFIRI = 5-FU/LV + irinotecan; CapeIRI = capecitabine (Xeloda) + irinotecan; IROX = irinotecan + oxaliplatin; CapeOx = capecitabine + oxaliplatin

Kozloff M, et al. Presented at: 2006 Gastrointestinal Cancers Symposium;

26–28 January 2006; San Francisco, Ca. Abstract 247

6.7

14.19.7

55.8

BRiTE: Avastin-relatedserious adverse events

Kozloff M, et al. Presented at: 2006 Gastrointestinal Cancers Symposium; 26–28 January 2006; San Francisco, Ca. Abstract 247

SAEs possibly related to Avastin No. of patients (%)(n=1,968)

Any 237 (12.0)

GI perforation 34 (1.7)

Postoperative bleeding or wound healing complication

24 (1.2)

ATE 41 (2.1)

Grade 3/4 bleeding 38 (1.9)

Other 60 (3.0)

ATE = arterial thromboembolic event; GI = gastrointestinal; SAE = serious adverse event

First-BEAT: most commonly usedchemotherapy regimens

30

25

20

15

10

5

0 Monotherapy Oxaliplatin Irinotecan Other/missing(16%) (47%) (33%) (4%)

5-FU bolus 8%

5-FU infusion 58%

Capecitabine 29%

Other 5%

Pe

rce

nta

ge

(%)

Van Cutsem E, et al. Presented at: 2006 Gastrointestinal Cancers Symposium; 26–28 January 2006; San Francisco, Ca. Abstract 250

First-BEAT: serious adverse events

Type Any SAE

n (%)Related* SAE

n (%)

Any SAE: patients, n (%)events, n

394 (25)638

132 (8)161

Febrile neutropenia 14 (0.9) 1 (0.1)

Deep vein thrombosis 19 (1.2) 16 (1.0)

Pulmonary embolism 18 (1.1) 16 (1.0)

Arterial thromboembolic events

11 (0.7) 9 (0.6)

Bleeding 19 (1.2) 13 (0.8)

GI perforation 20 (1.2) 11 (0.7)

Hypertension 8 (0.5) 8 (0.5)

Wound healing 5 (0.3) 5 (0.3)*Avastin related, Investigator assessment

Van Cutsem E, et al. Presented at: 2006 Gastrointestinal Cancers Symposium; 26–28 January 2006; San Francisco, Ca. Abstract 250

BRiTE and First-BEAT: summary

These ongoing observational studies are evaluating Avastin in combination with different chemotherapy regimens in a large population of patients with metastatic CRC

Avastin plus standard first-line chemotherapy is generally well tolerated, with a safety profile that is consistent with that observed in clinical trials

Data show that there are no new safety concerns for Avastin therapy in the clinical setting

ConclusionsAvastin improves survival in metastatic CRC when used first-line in combination with all standard chemotherapy regimens

Avastin should be considered as the critical first-line component to which chemotherapy is added

Avastin therapy should be continued until disease progression, irrespective of any modification to the concomitant chemotherapy regimen

Patients receiving Avastin experience progression-free and overall survival benefit even if they do not achieve an objective response to treatment, further supporting the use of Avastin until disease progression

Combination of Avastin with standard first-line chemotherapy is generally well tolerated

Addition of Avastin does not exacerbate toxicities associated with chemotherapy

Documents

Avastin ® : setting the standard in treatment for metastatic colorectal cancer (CRC) Fairooz Kabbinavar David Geffen School of Medicine at UCLA Los Angeles,