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ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

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Page 1: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Steering Committee meeting, 24th September 2005

University of Oxford Examination Schools

Page 2: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

ATLAS and aTTom

Update on current status

adjuvant Tamoxifen Treatment: offer more?

Page 3: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

ATLAS and aTTom study design

After several years on adjuvant tamoxifen, patient and doctor both SUBSTANTIALLY UNCERTAIN

about whether to stop now or continue

RANDOMISE

STOP tamoxifen now CONTINUE for at least 5 more years

Page 4: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Sample size sought

To confirm, or refute, a 3% difference in absolute survival (e.g. 75% to 78%), 8,000 patients would have to be randomised to have a 90% chance of detecting this difference (at a 5% statistical significance level) between the two groups.

To detect a 2% difference in absolute survival (e.g. 75% to 77%), 20,000 patients would be needed.

Page 5: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Completion of recruitment phase in ATLAS and aTTom

• January 2005: ATLAS Steering Committee (TSC) with the aTTom TSC decided to close accrual

• > 20,000 women now randomised in studies of 10 vs 5 years of tamoxifen

• aTTom and ATLAS closed to recruitment in March 2005.

Page 6: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

12898

2354

Page 7: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Number of patients randomised in ATLAS by country

30051730

16061466

942893890

784549

465319

292255254243

14714713813713211211092848276746855373733

0 500 1000 1500 2000 2500 3000 3500

IndiaSpainChile

BrazilCzech Republic

ArgentinaPoland

Australia/New ZealandHong Kong

EgyptRussia

ItalyTaiwan

IsraelIran

BelarusPeoples' Republic of China

USAJapan

BelgiumLithuania

CubaLatvia

South AfricaMexico

NetherlandsColombiaPortugal

TurkeyCroatiaEstonia5 others

Nam

e o

f co

un

try

Number of women randomised

15 254 women randomised from 30+ countries: largest cancer treatment trial so far!

Page 8: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Cumulative recruitment figures into aTTom by prior duration of tamoxifen

0

1000

2000

3000

4000

5000

6000

7000

8000

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005

Year of Randomisation

Cu

mu

lati

ve R

ecru

itm

en

t

<4 years prior tamoxifen

4+ years prior tamoxifen

Page 9: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

0

2000

4000

6000

8000

10000

12000

14000

Accrual in trials of 10 vs 5 years of tamoxifen

Page 10: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Baseline data of women randomised in ATLAS:

IdentifiersResponsible doctor

Patient name

Date of birth

Hospital number

National identification number

Address

Alternative contact details

ClinicalDate of diagnosis

ER status

Nodal status

Recurrence (including contralateral breast cancer)

Other primary cancer

Menopausal status

Ovarian ablation

Dose of tamoxifen (daily) and prior duration

Page 11: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

AGE DISTRIBUTION

0

1000

2000

3000

4000

5000

Number of women

randomised

Unknown <50 50-59 60-69 70+

Age (years)

Age distribution in "newer" component of ATLAS

STOP

CONTINUE

0

200

400

600

800

Number of women

randomised

<50 50-59 60-69 70+

Age (years)

Age distribution in "older" component of ATLAS

Page 12: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

0

2000

4000

6000

8000

Number of women

randomised

Node negative Node positive Unknown

Nodal status

Nodal status of women randomised in newer component of ATLAS

STOP

CONTINUE

0

500

1000

1500

Number of women

randomised

Node negative Node positive Unknown

Nodal status

Nodal status of women randomised in older component of ATLAS

NODAL STATUS

Page 13: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

ER status among women in ATLAS randomised after > 4

years of prior tamoxifen

10%

37%53%

ER poor

ER unknown

ER positive

ER status among women in ATLAS randomised after < 4

years of prior tamoxifen

9%

68%

23%

ER poor

ER unknown

ER pos itive

ER status

Page 14: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

ATLAS Older (n=2354) ER poor 9%ER unknown 68%ER positive 23%Newer (n=12898) ER poor 10%ER unknown 37%ER positive 53%

Distribution of ER status in ATLAS

Page 15: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

NB: Women in STOP and CONTINUE arms combined in each component ie – this is non-randomised

Survival among women in the “older” and “newer” components of ATLAS

Page 16: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Survival in ATLAS by nodal status

Page 17: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Survival in ATLAS by ER status

Page 18: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

ATLAS: the next few years

Compliance with random allocation

Completeness of follow-up

At present, women with a prior duration of 4 or more years of tamoxifen before randomisation have a median follow-up of ~3 years.

An absolute minimum of five more years of follow-up is needed for a proper assessment of the benefits and risks of long-term tamoxifen.

Page 19: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Numbers of women where follow-up should be data available

Number entered before 11/2004

Number entered from 11/2004

Total

<4 years pre-randomisationSubtotal:Mean follow-up (years):

4+ years pre-randomisationSubtotal:Mean follow-up (years):

23524.7

112542.5

20

6440

2354-

12898-

* Denominators for main breast cancer analysesH Denominators for main side-effect analyses

Page 20: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Compliance in older part of ATLAS

Page 21: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Compliance in newer part of ATLAS

Page 22: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Completeness of follow-up data

We must have up to date information on all women especially with respect to

- Compliance- Recurrence- Death (and if died, date and

cause of death)- Other primary cancers

Page 23: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Quality of follow-up data

• All forms should be completed in full!

• At least 80% of the ATLAS office’s time is spent chasing follow-up queries

Page 24: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Most common problems with follow-up forms

• Not returned!• Not completed in full• Doctors writing “Lost to follow-up”• Dates of events missing• Cause of death not provided• Hospital admission diagnosis and date missing

Page 25: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Use the information we have to help ensure long-term follow-up

IdentifiersResponsible doctorPatient nameDate of birthHospital numberNational identification number AddressAlternative contact details

Page 26: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

Summary

Long-term follow-up and good compliance are required in ATLAS:

If we can get these, we will get a reliable answer on whether longer versus shorter

tamoxifen improves survival among women

with early breast cancer

Page 27: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

0

2000

4000

6000

8000

10000

12000

14000

Page 28: ATLAS Steering Committee: 24 September 2005 Steering Committee meeting, 24 th September 2005 University of Oxford Examination Schools

ATLAS Steering Committee: 24 September 2005

I want to thank everyone personally for all they have done to make this collaboration work!

Dr Christina Davies, ATLAS Coordinator

For further information on any of this presentation, please contact [email protected]