atlas steering committee: 24 september 2005 steering committee meeting, 24 th september 2005...
TRANSCRIPT
ATLAS Steering Committee: 24 September 2005
Steering Committee meeting, 24th 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?
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
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.
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.
ATLAS Steering Committee: 24 September 2005
12898
2354
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!
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
ATLAS Steering Committee: 24 September 2005
0
2000
4000
6000
8000
10000
12000
14000
Accrual in trials of 10 vs 5 years of tamoxifen
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
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
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
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
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
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
ATLAS Steering Committee: 24 September 2005
Survival in ATLAS by nodal status
ATLAS Steering Committee: 24 September 2005
Survival in ATLAS by ER status
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.
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
ATLAS Steering Committee: 24 September 2005
Compliance in older part of ATLAS
ATLAS Steering Committee: 24 September 2005
Compliance in newer part of ATLAS
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
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
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
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
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
ATLAS Steering Committee: 24 September 2005
0
2000
4000
6000
8000
10000
12000
14000
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]