The Clinical Trials of HDC/ABMT in Women with

Breast Cancer

Prof Cindy FarquharMD MPHUniversity of Auckland, NZ

History The first RCTs commenced at the

end of 1990 Progress was slow Two US trials took years to

randomize 969 women 1990-1998 ASCO 1999: reports 4/5 RCTs no

benefit

The first published RCT Bezwoda 1995 - South African trial 3 year survival was 18% vs 4 % in

control group Small study (n=90) Event rate in the HDC/ABMT group

similar to US conventional treatment

American Society of Clinical Oncologists 1999

Results of 5 RCTs presented

Overall summary:

4/5 concluded “that treatment with HDC/ABMT is

no better than conventional chemotherapy”

Jan 2000 - the only trial (South African) to show

a benefit was declared fraudulent by the US

auditors (Bezwoda 1999)

Systematic review of HDC/ABMT in women with breast cancer

Aim: To determine the effectiveness and safety of HDC/ABMT in women with metastatic and high risk breast cancer

2 reviews : women with metastatic breast cancer women with high risk breast cancer

Methodology: systematic review

Systematic review All trials meet the inclusion criteria Assess the quality of the trials Trial results extracted for overall

survival, event free survival and treatment related mortality

Data was pooled using metanalysis

Excluded studies Bezwoda 1995, 1999 – declared

fraudulent in 2000 Bergh 2000 – overall dose in conventional

group higher than HDC/ABMT group Peters 1996 - – control group crossed over

to HDC/ABMT Madan 2000 – control group crossed over

to HDC/ABMT

Metastatic Breast Cancer: included studies

Study name Country Study accrual completed

Number of participants

Eastern Coop Onc Group

US 1997 199

NCI of Canada Canada 2000 219

PEGASE 03 France 2000 180

PEGASE 04 France 1996 61

Schmid Germany 2001 92

IBDIS International 2001 101

HDC/ABMT in women with metastatic BC: treatment related mortality

Increased by standard chemotherapy Increased by HDC/ABMT

HDC in women with metastatic BC: event free survival 1 year follow up

5 year follow up

Increased by standard chemotherapy Increased by HDC/ABMT

3 year follow up

HDC in women with metastatic BC: overall survival 3 year follow up

5 year follow up

Increased by standard chemotherapy Increased by HDC/ABMT

High Risk Breast Cancer: included studiesStudy Name Country Accural Date No. of women

ACCOG 1 UK 6/99 605

CALGB US 5/98 783

Dutch Pilot Netherlands 12/95 81

Dutch I Group Netherlands 7/99 885

GABG Germany 11/97 302

ECOG US 1998 93

JCOG Japan 1999 97

ICCG International 2000 281

IBCSG International 2002 344

MDACC US 12/98 78

MCG Italy 1998 398

PEGASE 01 France 12/98 314

WSG Germany 2002 403

HDC in women with high risk BC: treatment related mortality

Increased by standard chemotherapy Increased by HDC/ABMT

HDC in women with high risk BC: event free survival 3 year follow up

5 year follow up

Increased by standard chemotherapy Increased by HDC/ABMT

HDC in women with high risk BC: overall survival

3 year follow up

5 year follow up

Increased by standard chemotherapy Increased by HDC/ABMT

Overall 67% of women survived in HDC group and 71% in the control group

Quality of Life Measures

ACCOG : 84 women on HDC/ABMT and 82 standard dose. no difference b/w groups at 6 or 12 months

CALBG: 106 HDC/ABMT and 104 standard dose. HDC worse at 3 months, but no difference at 12 months

Dutch IG trial: HDC/ABMT lower scores at 3 months but no difference at 6 months. Also looked at cognitive functioning in Dutch IG:

significantly impaired in HDC/ABMT

Conclusions: women with metastatic breast cancer

Treatment related mortality was significantly increased

At one year of follow up there is a increase in event free survival in women with HCD/ABMT

At three and five years of follow up there is no impact on either event free survival or overall survival

Conclusions: women with high risk breast cancer

Treatment related mortality was significantly increased

At three years of follow up there is a reduction in event free survival but no impact on overall survival

At five years of follow up there is no impact seen on either event free survival or overall survival

Acknowledgements The Commonwealth Fund of New

York Robert Wood Johnson Foundation RAND University of Auckland, NZ The Cochrane Breast Cancer Group