david miles chair at the mount vernon cancer centre, middlesex, uk

David MilesChair at the Mount Vernon Cancer Centre,

Middlesex, UK Past Senior Lecturer and Consultant

in Medical Oncology at Guy’s and St Thomas’ Hospital, London

Received awards from the British Association of Cancer Research, the American Society of Clinical Oncology and the American Association for Cancer Research

Published numerous papers on breast cancer and biological therapies

On Institutional Review Board for Cancer Research UK and UK National Institute for Clinical Excellence committee for the treatment of early stage breast cancer

Mount Vernon Hospital

Innovation + strength = effective management for HER2-negative

metastatic breast cancer

David MilesMount Vernon Hospital

Middlesex, UK

Introduction

Breast cancer is the leading cause of cancer mortality in women worldwide

Improvements in detection and therapy of early breast cancer have greatly improved survival– many patients still go on to develop recurrent or

metastatic disease

Aims of therapy for systemic disease– slow/halt disease progression– extend survival– maintain patient QoL through symptom relief

QoL = quality of life

Potentially hormone responsive

CYTOTOXIC CHEMOTHERAPY WITH OR WITHOUT TRASTUZUMAB

Postmenopausal

Ov Abl Tamoxifen Tamoxifen

AI

on progression

Metastatic breast cancer (MBC)Aggressive visceral disease

Other metastatic patterns

Premenopausal

No response Ov Abl AI

No responseor on

progression

Ov Abl = ovarian ablation; AI = aromatase inhibitor

VinorelbineVarious

Changing options in MBC (1980s)

Anthracyclines

Taxanes Capecitabine

SERMS(tamoxifen)

AIs(letrozole)

SERDS(faslodex)

First line Second lineThird line

SERMS = selective oestrogen-receptor modulatorsSERDS = selective oestrogen-receptor down regulators

VinorelbineVarious


Anthracyclines


SERMS(tamoxifen)

AIs(letrozole)

SERDS(faslodex)

First lineSecond line

± trastuzumab

VinorelbineVarious


Anthracyclines


SERMS(tamoxifen)

AIs(letrozole)

SERDS(faslodex)

First line

± trastuzumab

Treatment scenario 1

You are treating a patient with the following characteristics

– 62-year-old woman

– HER2-negative, hormone receptor-negative MBC

• metastasis to bone

– no prior chemotherapy for metastatic disease

– adjuvant therapy with both doxorubicin and paclitaxel2 and a half years previously

• did not tolerate taxane well (neuropathy)

What treatment would you recommend?

Capecitabine

Intestine

Liver

Capecitabine

CE

5'-DFCR

CyD

5'-DFUR

Tumour

5'-DFCR

CyD

5'-DFUR

5-FU

Thymidinephosphorylase (TP)

5'-DFCR = 5'-deoxy-5-fluorocytidine; 5'-DFUR = 5'-deoxy-5-fluorouridine;CyD = cytidine deaminase; CE = carboxyl esterase; 5-FU = 5-fluorouracil

Enzymatic activation of capecitabine

More 5-FU in the tumour with TP-activated capecitabine

Schüller J, et al. Cancer Chemother Pharmacol 2000;45:291–7

Normal tissue

*Ratio of median values

5-FU

5-FU

5-FU

5-FU

Tumour tissue

5-FU

5-FU 5-FU5-FU

5-FU

5-FU

5-FU5-FU

5-FU

Plasma

x 3.2* x 21.4*

Capecitabine monotherapy has activity in first-line MBC (phase II trials)

TrialC dose (mg/m2,

twice daily)RR (%)

Median TTP (months)

Median OS (months)

O’Shaughnessy et al.1 C1,250

(n=61) 30 4.1 19.6

Soto et al.2 C1,250

(n=91) 46 8.4*,† 24+*

Bajetta et al.3

C1,250

(n=30) 37 3.9 10

C1,000

(n=43) 35 4.1 16

1O’Shaughnessy J, et al. Ann Oncol 2001;12:1247–542Soto C, et al. J Clin Oncol 2006;24(Suppl. 18):20s (Abstract 570)

3Bajetta E, et al. J Clin Oncol 2005;23:2155–61

*Includes patients receiving a taxane following capecitabine monotherapy; †PFS

C = capecitabine; RR = response rate;TTP = time to progression; OS = overall survival;PFS = progression-free survival

Key phase III trial of first-linecapecitabine monotherapy versus oral CMF

Primary endpoints: PFS (efficacy), quality-adjusted PFS (effectiveness)

Secondary endpoints: RR, health-related QoL, OS and safety

MBC patients unsuitable for

intensive chemotherapy

Stratified for institution, PS, liver or brain metastases,

planned use of bisphosphonates/

prednisone

Continuous capecitabine650mg/m2 b.i.d., days 1–21, every 3 weeks

Intermittent capecitabine1,000mg/m2 b.i.d., days 1–14, every 3 weeks

Classical CMFOral cyclophosphamide 100mg/m2 days 1–14i.v. methotrexate 40mg/m2 days 1, 8 i.v. 5-FU 600mg/m2 day 1, 8, every 4 weeks

RANDO MISATION

b.i.d. = twice daily; i.v. = intravenous; CMF = cyclophosphamide, methotrexate and 5-FU; PS = performance status

Stockler MR, et al. J Clin Oncol 200725(Suppl. 18):39s (Abstract 1031)

Capecitabine versus CMF baseline characteristics: a relatively young, fit

population

%Int C

(n=107)Cont C (n=107)

CMF (n=109)

Age <60 60

3664

4753

4456

ECOG 0–1 88 88 86

Liver/brain metastases 45 48 47

Diagnosis advanced disease 4y 56 52 56

ER+ or PR+ 62 67 64

Adjuvant chemotherapy CMF AC+CMF AC Taxane

1910 6 2

20 9 5 4

21 7 5 4

Prior endocrine therapy 78 82 79

Stockler MR, et al. J Clin Oncol 200725(Suppl. 18):39s (Abstract 1031)

Int = intermittent; Cont = continuousECOG = Eastern Cooperative Oncology Group

Capecitabine versus CMF: similarresponse rates

%Int C

(n=107)Cont C (n=107)

CMF (n=109)

Overall RR Complete (CR) Partial (PR)

22 418

20 020

18 117

Stable disease (SD) 39 46 41

Disease control rate (CR+PR+SD) 61 66 59

Patients receiving therapy for 12 months 19 17 5

Stockler MR, et al. J Clin Oncol 2007;25(Suppl. 18):39s (Abstract 1031)

Capecitabine versus CMF: significantsurvival benefit with capecitabine

Median (months)

Capecitabine (intermittent)+ continuous 22

CMF 18

0 6 12 18 24 30 36 42 48Months

1.0

0.8

0.6

0.4

0.2

0

Pro

po

rtio

n a

live

HR = hazard ratio; CI = confidence interval

Log-rank p=0.02HR=0.72 (95% CI: 0.55–0.94)


Capecitabine monotherapy is well tolerated

Intermittent capecitabine

Continuous capecitabine

CMF

*

*

**

†

*p≤0.0001 X versus CMF;†p=0.03 X versus CMF

Gra

de

3/4

adve

rse

even

ts (

%)


50

40

30

20

10

0

Hand-fo

ot

syndro

me

Neutro

penia

Febril

e

neutro

penia

Stom

atiti

s

Infe

ctio

n

Alopec

ia

Other

toxi

citie

s

Capecitabine monotherapy has proven efficacy across all lines of therapy

ORR (%)

Median TTP (months)

Median OS (months)

Anthracycline and taxane naïve1–3 22–37 3.9–4.1 10.0–24.0

Anthracycline pretreated4,5 36–46 3.0 7.6

Anthracycline and taxanepretreated6–11 15–28 3.0–5.0 10.1–15.9

1Stockler MR, et al. J Clin Oncol 2007;25(Suppl. 18):39s (Abstract 1031) 2Bajetta E, et al. J Clin Oncol 2005;23:2155–61

3O’Shaughnessy J, et al. Ann Oncol 2001;12:1247–54; 4Talbot D, et al. Br J Cancer 2002;86:1367–725Soto C, et al. J Clin Oncol 2006;24(Suppl. 18):20s (Abstract 570)

6Blum J, et al. J Clin Oncol 1999;17:485–937Largillier R, et al. Ann Oncol 2006;17(S9) (Abstract 161P); 8Miller K, et al. J Clin Oncol 2005;23:792–9

9Mavroudis D, et al. J Clin Oncol 2006;24(Suppl. 18):42s (Abstract 658) 10Reichardt P, et al. Ann Oncol 2003;14:1227–33; 11Blum J, et al. Cancer 2001;92:1759–68

ORR = overall response rate

Capecitabine plus docetaxel first line significantly extends TTP: pivotal clinical trial

4.2 6.1

CD (n=255)

Docetaxel (n=256)

Log-rank p=0.0001; HR=0.652

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28

Est

imat

ed p

rob

abil

ity

Months

O’Shaughnessy J, et al. J Clin Oncol 2002;20:2812–23

1.0

0.8

0.6

0.4

0.2

0

CD = capecitabine + docetaxel

Capecitabine plus docetaxel first line significantly extends OS: pivotal clinical trial

Miles D, et al. Clin Breast Cancer 2004;5:273–8Minimum follow-up = 27 months

11.5 14.5

CD Docetaxel

Log-rank p<0.01; HR=0.777

0 4 8 12 16 20 24 28 32 36 40 44 48

Est

imat

ed p

rob

abil

ity

Months

1.0

0.8

0.6

0.4

0.2

0

CD: most common (>5%) grade 3/4 treatment-related toxicities

Stom

atiti

s

50

40

30

20

10

0

Pat

ien

ts (

%)

Diarrh

oea

Hand-fo

ot

syndro

me

Nause

a

Fatig

ue/

asth

enia

Neutro

penic

feve

r

CD (n=251)

Docetaxel (n=255)

Grade 3Grade 4

Grade 3Grade 4

O’Shaughnessy J, et al. J Clin Oncol 2002;20:2812–23

Failure, or resistance to an anthracycline-based

therapy given in the neoadjuvant, first or

second-line metastatic setting

and

two non-adjuvant regimens of

chemotherapy

Phase III trial of capecitabine with docetaxelin anthracycline-resistant MBC (NO16853)

RANDO MISATION

Primary endpoint: equivalency in TTP or death

Planned sample size: 440 patients

Capecitabineb.i.d. 950mg/m2 day 1–14 every 3 weeks

Docetaxel75mg/m2 (60 minute) i.v.day 1 every 3 weeks

Capecitabineb.i.d. 1,250mg/m2 days 1–14 every 3 weeks

Docetaxel75mg/m2 (60 minute) i.v. day 1 every 3 weeks

Treatment scenario 2

You are treating a patient with the following characteristics– HER2-negative, hormone receptor-negative MBC– no prior chemotherapy for metastatic disease– relatively young (45 years), with good PS– adjuvant therapy with anthracyclines, 3–4

years previously

What treatment would you recommend?

Angiogenesis is essentialfor tumour growth

Adapted from Poon RT, et al. J Clin Oncol 2001;19:1207–25

Stages at which angiogenesis plays a role in tumour progression

Premalignanttumour

Malignanttumour

Tumourgrowth

Vascularinvasion

Micro-metastases

Metastaticgrowth

Angiogenicswitch

Bevacizumab binds VEGF,the key mediator of angiogenesis

Recombinant humanised monoclonal anti-VEGF antibody

– humanised murine antibody(93% human, 7% murine)

• prevents possible immune reactions

– recognises and binds to all major isoforms of human VEGF-A

• prevents VEGF from interacting with its receptors

• results in the inhibition of activation of downstream signalling pathways

– terminal half-life = 17–21 days

• enables convenient combination with concomitant therapy schedules

Bevacizumab

– P– P

P– P–

VEGF

X

Growth

Proliferation

Migration

Survival

X

VEGF = vascular endothelial growth factor

Phase III trial of bevacizumab plus capecitabine in pretreated MBC (AVF2119g)

Primary endpoint: PFS– secondary endpoints: ORR and OS

*Prior anthracycline and taxane treatment– one or two prior chemotherapy regimens for MBC, or– relapse within 12 months of completing anthracycline- and

taxane-containing adjuvant therapy

Previously treated MBC* (n=462)

Capecitabine (n=230)

Capecitabine + bevacizumab 15mg/kg every 3 weeks (n=232)

Treat to disease progression

Treat to disease progression†

†No cross over was permitted

Capecitabine1,250mg/m2 orally b.i.d. for2 weeks of a 3-week cycle

Miller KD, et al. J Clin Oncol 2005;23:792–9

AVF2119g: patient characteristics

Key baseline patient characteristicsCapecitabine

(n=230)

Bevacizumab + capecitabine

(n=232)

Prior chemotherapy exposure in the metastatic setting (%) 83.9 84.9

One chemotherapy regimen (%) 42.6 46.1

Two or more chemotherapy regimens (%) 41.3 38.8

Prior trastuzumab (%) 23.9 25.0

Prior myeloablative therapy (%) 10.0 9.1

≥3 metastatic sites (%) 50.4 49.1

Visceral disease (%) 80.0 77.6

Miller KD, et al. J Clin Oncol 2005;23:792–9

AVF2119g: efficacy summary

The addition of bevacizumab to capecitabine more than doubled the response rate according to an independent review facility

Capecitabine(n=230)

Bevacizumab + capecitabine (n=232) p value

Overall response rate (%)

Investigators

Independent review facility

19.1

9.1

30.2

19.8

0.006

0.001

Median PFS (months) 4.2 4.9 NS

Median OS (months) 14.5 15.1 NS

NS = not significant Miller KD, et al. J Clin Oncol 2005;23:792–9

AVF2119g: grade 3/4 adverse events

*No grade 4

Adverse eventCapecitabine

(n=215)Bevacizumab +

capecitabine (n=229)

Hypertension* 0.5 17.9

Proteinuria* 0.0 0.9

Thrombosis 3.7 5.6

Hand-foot syndrome* 24.2 27.5

Bleeding* 0.5 0.4

CHF/cardiomyopathy 1.0 3.0

Nausea* 1.9 2.6

CHF = congestive heart failure Miller KD, et al. J Clin Oncol 2005;23:792–9

Angiogenesis: redundancy in the system

Adapted from Folkman J. In: DeVita VT, et al. editors. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2005. p. 2865–82

Bevacizumab may be more effective earlier in thecourse of MBC

VEGFVEGFbFGFTGF-1

VEGFbFGFTGF-1PlGF

VEGFbFGFTGF-1PlGFPD-ECGF

VEGFbFGFTGF-1PlGFPD-ECGFPleiotrophin

Breast cancer

Tumour growth

E2100: phase III trial of first-line paclitaxel ± bevacizumab in MBC

Primary endpoint: PFS

Other endpoints: ORR, OS, QoL

Miller KD, et al. N Engl J Med 2007;357:2666–76

Previously untreated locally recurrent or

MBC(n=722)

Paclitaxel(n=354)

Paclitaxel + bevacizumab

10mg/kg every 2 weeks(n=368)

Treat to disease progression*


*No cross over permitted

Paclitaxel:90mg/m2 every week for 3 weeks of a 4-week cycle

*No cross over permitted

E2100: statistical design

Primary endpoint: PFS– 85% power for a 33% improvement

• 6 vs 8 months

Final analysis after 546 PFS– interim analyses after 270 and 425 events

Safety analyses– grade 4 haemorrhage or hypertension

(1% acceptable)– grade 3/4 thrombosis or embolism (5% acceptable)

Miller KD, et al. N Engl J Med 2007;357:2666–76

E2100: treatment arms were well balanced for major prognostic factors

Paclitaxel (n=354)

Bevacizumab + paclitaxel (n=368)

Median age, years (range) 55 (27–85) 56 (29–84)

ER-positive, n (%) 223 (63.0) 223 (60.6)

PR-positive, n (%) 158 (44.6) 166 (45.1)

HER2-positive, n (%) 5 (1.4) 2 (0.5)

Disease-free interval, n (%) 24 months>24 months

146 (41.2)208 (58.8)

150 (40.8)

218 (59.2)

Number of metastatic sites, n (%)<33

252 (71.2) 102 (28.8)

262 (71.2)

106 (28.8)

Prior taxane therapy, n (%) 68 (19.2) 74 (20.1)

Prior anthracycline therapy, n (%) 180 (50.8) 184 (50.0)

ER-positive = oestrogen receptor-positive; PR-positive = progesterone receptor-positive Data on file submitted to CHMP November 07

Bevacizumab plus paclitaxel (E2100): PFS benefitconfirmed by Independent Review Facility (IRF)

11.4

0 6 12 18 24 30 36

PF

S e

stim

ate

5.8 11.3

5.8

Months

1.0

0.8

0.6

0.4

0.2

0

*Scans available for 90% of patients

n PFS by HR

Paclitaxel 354 Investigator0.42

Bevacizumab + paclitaxel 368 Investigator

Data on file submitted to CHMP November 07

Paclitaxel 354 IRF*0.48

Bevacizumab + paclitaxel 368 IRF*

Bevacizumab plus paclitaxel (E2100):consistent PFS benefit in subgroup analysis

Increase inmedian PFS (%)

103

114

126

113

98

55

116

73

Prior adjuvant hormonetherapy (n=343)

Prior adjuvantchemotherapy (n=475)Prior adjuvant taxane

therapy (n=142)Prior adjuvant anthracycline

therapy (n=364)Prior metastatic hormone

therapy (n=262)

ER-positive status (n=446)

24-month disease-freeinterval (n=296)

3 metastatic sites(n=208)

9 monthsMedian PFS*

Months0 5 10 15

*PFS as assessed by IRF

Paclitaxel Bevacizumab + paclitaxel

6.1

5.8

5.8

6.0

6.0

7.7

4.9

4.8

12.4

12.4

13.1

12.8

11.9

11.9

10.6

8.3


Bes

t re

spo

nse

(%

)

E2100: objective response(patients with measurable disease)

Investigator assessment

(n=525)

IRF assessment(n=472)

50

2223

48

Paclitaxel

Bevacizumab

+ paclitaxel

CR + PRp<0.0001

CR + PRp<0.0001


60

50

40

30

20

10

0

E2100: increased survival with bevacizumab was seen over the first 30 months

1.0

0.8

0.6

0.4

0.2

00 6 12 18 24 30 36 42 48 54 60

*Post-hoc

p=0.017*

74.0%

81.4%

50.1%

55.0%

p=0.191*

Log-rank p=0.1374; HR=0.869 (95% CI: 0.722–1.046)

Median OS n (months)

Bevacizumab + paclitaxel 368 26.5

Paclitaxel 354 24.8

OS

est

imat

e

MonthsData on file submitted to CHMP November 07

80% power to detect OS 24–31 months

10–15% power to detect OS of 3 months

E2100: increased survival with bevacizumab was seen over the first 30 months

1.0

0.8

0.6

0.4

0.2

00 6 12 18 24 30 36 42 48 54 60

OS

est

imat

e

Months

Median OS n months

Bevacizumab + paclitaxel 368 26.5

Paclitaxel 354 24.8


E2100: most frequent grade 3adverse events (5% incidence)

#Includes NCI AdEERS mandatory collection in the bevacizumab + paclitaxel arm only, which does not allow valid comparison between the two arms

Data on file submitted to CHMP November 07 NCI-CTCAE = National Cancer Institute-Common Terminology Criteria for Adverse Events

NCI-CTCAE term

Paclitaxel (n = 348)

(%)

Paclitaxel + bevacizumab#

n = 363, (%)

Difference

(%)

Patients with 1 event 50.6 71.1 20.5

Neuropathy 17.5 24.2 6.7

Hypertension 1.4 16.0 14.6

Fatigue 5.2 10.7 5.5

Infection without neutropenia

4.6

9.1

4.5

Neutropenia (grade 4) 3.2 5.8 2.6

Vomiting 2.3 5.5 3.2

Less frequently reportedbevacizumab-related adverse events

CHF/cardiomyopathy– observed in 2.2% of patients treated with bevacizumab plus paclitaxel– caution should be exercised with patients experiencing clinically significant

cardiac disease

ATE and VTE– observed in 3.6% and 3.0% of patients treated with bevacizumab plus paclitaxel– discontinue bevacizumab in patients with symptomatic pulmonary embolism

and those who develop ATE

Wound-healing complications– severe wound-healing complications were observed in 1.1% of patients treated

with bevacizumab plus paclitaxel– bevacizumab should not be initiated for ≥28 days following major surgery or in

patients with unhealed wounds, and should be withheld for elective surgery

GI perforations– observed in <1% of patients treated with bevacizumab plus paclitaxel – permanently discontinue bevacizumab in patients experiencing GI perforation

Data on file submitted to CHMP November 07; Avastin Summary of Product Characteristics (SmPC)

E2100: quality of lifeM

ean

ch

ang

e fr

om

bas

eli

ne

Worse

BetterTOI-B

p=0.0006 (primary analysis)

Baseline Week 17 Week 33

73

–1–5–9

–13–17–21–25–29–33–37–41

p=0.0001

Mea

n c

han

ge

fro

m b

ase

lin

e

Worse

BetterTOT-B

p<0.0001

p=0.0001

Baseline Week 17 Week 33

Bevacizumab+ paclitaxelPaclitaxel

Roche data on file submitted to regulatory authority in 2006

73

–1–5–9

–13–17–21–25–29–33–37–41

TOI-B (Trial Outcome Index) incorporates measures of physical, functional and breast cancer-specific quality of life

TOT-B (Total Score) includes emotional and social/family well-being in addition to the above

E2100: summary

Substantial prolongation of PFS– living without the disease advancing and improving

disease-related symptoms– delaying subsequent lines of therapy and

associated side effects

Higher QoL

Superior 1-year survival

Positive risk:benefit ratio

Bevacizumab plus docetaxel in first-line MBC (AVADO): phase III study design

Recruitment completed in March 2007

– target recruitment was exceeded and 736 patients have been enrolled

Primary endpoint: PFS

– secondary endpoints: ORR, OS, safety, QoL

Data to be presented at ASCO 2008

Previously untreated HER2-negative locally recurrent or

MBC (n=705)

Docetaxel 100mg/m2 every 3 weeks + placebo

Treat todisease

progression

Docetaxel + bevacizumab7.5mg/kg every

3 weeks

Docetaxel + bevacizumab15mg/kg every

3 weeks

PI: David Miles

Treat todisease

progression

Treat todisease

progression

Phase III trial of bevacizumab plus chemotherapy in first-line MBC (RIBBON 1)

Recruitment completed August 2007

Primary endpoint: PFS– secondary endpoints: chemotherapy-specific PFS, objective

response rate, OS, safety

*Continuation or cross over to bevacizumab is allowed at the discretion of the investigator

1

2

Randomisation

PI: Joyce O’Shaughnessy

Anthracycline-based or taxane or capecitabine + bevacizumab 15mg/kg

every 3 weeks

Anthracycline-based or taxane or

capecitabine + placebo


Previously untreated

MBC (n=1,239)


Safety study of bevacizumab plus chemotherapy in first-line MBC (MO19391)

Recruitment started Q3 2006– planned in 510 centres from 38 countries worldwide

Primary endpoint: safety– secondary endpoints: time to disease progression, OS, safety

in patients with CNS metastases

Previously untreated HER2-negative locally

recurrent or MBC(n~2,300)

Bevacizumab (10mg/kg every 2 weeks or

15mg/kg every 3 weeks)+

taxane-based chemotherapy*

Treat to disease

progression

PI: Ian Smith

*Taxane use according to routine practice or, if taxanes contraindicated, alternative chemotherapy allowed at physician’s discretionCNS = central nervous system

Smith IE, et al. Eur J Cancer Suppl2007;5:221 (Abstract 2123)

Rationale for combining bevacizumab with hormonal therapy

Evidence suggests that oestrogen directly modulates angiogenesis– regulatory regions of the VEGF gene contain elements

responsive to oestrogen1

– oestrogen upregulates VEGF expression in a breast cancer cell line2

– aromatase inhibitors decrease VEGF levels in a rat model3

The combination of bevacizumab and fulvestrant produced considerably greater growth suppression of breast cancer xenografts than either agent alone4

1Hyder SM, et al. Cancer Res 2000;60:3183–90; 2Takei H, et al. Breast Cancer 2002;9:39–423Nakamura J, et al. Endocrinology 1996;137:5589–96

4Pietras RJ, et al. Breast Cancer Res Treat 2006;100(Suppl. 1):S37 (Abstract 507)

Trials of bevacizumab combined with hormonal therapies in MBC

GEICAM 2006-11: phase III study of bevacizumab + letrozole

ER+/PR+ previously untreated locally recurrent or MBC

(n~360)

Aromatase inhibitor or tamoxifen +

bevacizumab 15mg/kg q3w

Aromatase inhibitor or tamoxifen + placebo



CALGB 40503: phase III trial of bevacizumab + endocrine agents

Primary endpoint: progression-free survival, response assessment every9 weeks

Postmenopausal women with advanced or MBC suitable for

endocrine therapy

Letrozole

Letrozole + bevacizumab15mg/kg q3w



Primary endpoint: progression-free survival

Summary

Bevacizumab and capecitabine play integral roles in the treatment algorithm for HER2-negative MBC

Bevacizumab plus paclitaxel is effective and well tolerated and is suitable for most patients with MBC

Single-agent capecitabine has demonstrated efficacy across all lines of MBC therapy

Data from ongoing studies will further expand the use of these agents in MBC

david miles chair at the mount vernon cancer centre, middlesex, uk

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