sabcs12 atlas pdf

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2012

S1-2. ATLAS 10 v 5 years of adjuvant tamoxifen

(TAM) in ER+ disease: Effects on outcome in the firstand in the second decade after diagnosis

Dr. Davies has no relevant financial relationshipsto disclose

Dr. Pan has no relevant financial relationships

to disclose Dr. Godwin has no relevant financial relationships

to disclose Dr. Gray has no relevant financial relationships

to disclose

Dr. Peto has no relevant financial relationshipsto disclose


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ATLAS - Adjuvant Tamoxifen: Longer Against Shorter

10 vs 5 years of adjuvant tamoxifen in ER+ disease:effects in the first & second decade after diagnosis

Presented on behalf of the

ATLAS collaborative group

All authors declare no relevant conflict of interest.

San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012

This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.


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ER+ breast cancer: 15-year effects of adjuvant

tamoxifen on recurrence & breast cancer mortality

5 years of adjuvant tamoxifen vs none:

Previously published EBCTCG meta-analysis

10 years of adjuvant tamoxifen vs 5 years:ATLAS trial, LancetDecember 5, 2012*

* http://dx.doi.org/10.1016/S0140-6736(12)61963-1




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Long-term effects of continuing adjuvant tamoxifen to 10 years vs

stopping at 5 years after diagnosis of oestrogen receptor-positive

breast cancer: ATLAS, a randomised trial

Christina Davies, Hongchao Pan, Jon Godwin, Richard Gray, Rodrigo Arriagada, Vinod Raina, Mirta Abraham, Victor Hugo Medeiros Alencar,Atef Badran, Xavier Bonfill, Joan Bradbury, Michael Clarke, Rory Collins, Susan R Davis, Antonella Delmestri, John F Forbes, Peiman Haddad,

Ming-Feng Hou, Moshe Inbar, Hussein Khaled, Joanna Kielanowska, Wing-Hong Kwan, Beela S Mathew, Bettina Mller, Antonio Nicolucci,

Octavio Peralta, Fany Pernas, Lubos Petruzelka, Tadeusz Pienkowski, Balakrishnan Rajan, Maryna T Rubach, Sera Tort, Gerard Urrtia,

Miriam Valentini, Yaochen Wang, Richard Peto, for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group*

SummaryBackground For women with oestrogen receptor (ER)-positive early breast cancer, treatment with

tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years

instead of stopping at 5 years.

Interpretation For women with ER-positive disease, continuing tamoxifen to 10 years rather than

stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10.

These results, taken together with results from previous trials of 5 years of tamoxifen treatment versusnone, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality

during the second decade after diagnosis.

Funding Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU Biomed.

www.thelancet.comPublished online Dec 5, 2012 http://dx.doi.org/10.1016/S0140-6736(12)61963-1




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ER+ early breast cancer: 15-year effects of

tamoxifen on recurrence & breast cancer mortality

5 years of adjuvant tamoxifen vs none:Previously published EBCTCG meta-analysis

10 years of adjuvant tamoxifen vs 5 years:ATLAS trial, LancetDecember 5, 2012*

* http://dx.doi.org/10.1016/S0140-6736(12)61963-1




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*EBCTCG, Lancet2011; 378: 77184San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.

5 years of tamoxifen versus no tamoxifen*

RECURRENCE BREAST CANCER MORTALITY

ER+ ER+


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ER+ disease, 5 yrs tamoxifen vs no tamoxifen

Breast cancer death rate ratio (RR), by period

5 yrs tam. vs 0:

meta-analysis

(n=10 645)

- years 0-4 0.71(0.62-0.80)

- years 5-9 0.66(0.58-0.75)

- years 10+ 0.73(0.62-0.86)




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10 years of tamoxifen vs 5: ATLAS(Adjuvant Tamoxifen - Longer Against Shorter)

6846 women with ER+ disease completed 5

years of tamoxifen, then were randomised to:

CONTINUE to year 10,or STOP at year 5.




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10 years of tamoxifen vs 5


years of tamoxifen, then were randomised:


25% Asia/mid-East, 28% Latin America,

47% Europe/US/ANZ/South Africa

54% node-negative

8 yrs follow-up: compliance, recurrence, deathSan Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012



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Recurrence: 617 vs 711 women (2p=0.002)

Breast cancer mortality: 331 vs 397 (2p=0.01)

Overall mortality: 639 vs 722 (2p=0.01)

San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.


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Recurrence and breast cancer mortality:

Little effect during years 5-9;

benefit mainly after year 10

San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.


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ATLAS: 6846 women, ER+, 10 vs 5 years tamoxifen

RECURRENCE BREAST CANCER MORTALITY


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ER+ disease, 5 yrs tam. vs 0, and 10 yrs vs 5 yrs.


5 yrs tam. vs 0:

meta-analysis

(n=10 645)

10 yrs tam. vs 5:

ATLAS trial

(n=6846)

- years 0-4 0.71(0.62-0.80) (1.0)

- years 5-9 0.66(0.58-0.75) 0.97 (0.79-1.18)

- years 10+ 0.73(0.62-0.86) 0.71 (0.58-0.88)



p=0.0016


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ER+ disease, 5 yrs tam. vs 0, and 10 yrs vs 5 yrs.


5 yrs tam. vs 0:meta-analysis

(n=10 645)

10 yrs tam. vs 5:ATLAS trial

(n=6846)

10 yrs tam. vs 0(estimated as

product of RRs)

- years 0-4 0.71(0.62-0.80) (1.0) 0.71 (0.62-0.81)

- years 5-9 0.66(0.58-0.75) 0.97 (0.79-1.18) 0.64 (0.50-0.82)

- years 10+ 0.73(0.62-0.86) 0.71 (0.58-0.88) 0.52 (0.40-0.68)



10 yrs tam. reduces breast cancer mortality by

a third in first decade & half in second decade

p=0.0016


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Trials under-estimate real benefits

Analyses by allocated treatment suggest that

10 yrs tam. reduces breast cancer mortality by

a third in first decade & half in second decade,

so actual use of 10 yrs tam. has a greater effect.

5 yrs tam vs 0: compliance after 2 years ~80%

10 yrs tam vs 5 (ATLAS): at 2 yrs, 84% vs 4% use(difference in proportions using tam. ~80%)


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Compliance: 2 years after ATLAS randomisation,

84% of CONTINUE versus 4% of STOP were taking

tamoxifen (80% difference between proportions)




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Side effects and main effects of 10 yrs tam. on

15-yr mortality in meta-analysis & ATLAS trial

5 yrs tam. vs 0:

meta-analysis

10 yrs tam. vs 5:

ATLAS trial

10 yrs tam. vs 0

(by addition)

Endometrial

cancer & PEmortality

0.2% loss 0.2% loss 0.4% loss

Breast

cancer

mortality

9% gain 3% gain 12% gain



Estimated effects of 10 yrs tam. vs 0 on 15-yr

mortality: absolute gain ~30x absolute loss


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Further research

- 2013: aTTom (UK counterpart of ATLAS)- 2013: EBCTCG meta-analysis of 10 vs 5 yr

- 2017: 5 more years of ATLAS follow-up

Generalizability to other endocrine drugs of

later benefit from 10 vs 5 years treatment?


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San Antonio Breast Cancer Symposium

Cancer Therapy and Research Center at UT

Health Science Center December 4-8, 2012

This presentation is the intellectual property

of ATLAS. Contact [email protected] for

permission to reproduce or distribute.


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ER+ disease: effects of adjuvant tamoxifen duration on breast cancer mortality

Left: 5 years tam. vs none (EBCTCG meta-analysis), Right: 10 vs 5 years (ATLAS)

Group allocated ~5y tamoxifen:

15.0% die between years 5-15




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ER+ disease: Effects of tamoxifen duration on

event rate ratio (RR), by time since diagnosis

5 years tam. vs none:EBCTCG meta-analysis

(n=10 645)

Recurrence in:

- years 0-4 RR=0.53 (0.48-0.57)

- years 5-9 0.68 (0.60-0.78)

- years 10+ 0.94 (0.79-1.12)




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(n=10 645)

Recurrence in:

- years 0-4 RR=0.53 (0.48-0.57)

- years 5-9 0.68 (0.60-0.78)

- years 10+ 0.94 (0.79-1.12)

Breast cancer

mortality in:

- years 0-4 0.71 (0.62-0.80)

- years 5-9 0.66 (0.58-0.75)

- years 10+

0.73 (0.62-0.86)

2p=0.0001




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(n=10 645)

10 years tam. vs 5:ATLAS trial

(n=6846)

Recurrence in:

- years 0-4 RR=0.53 (0.48-0.57) (1.0)

- years 5-9 0.68 (0.60-0.78) 0.90 (0.79-1.02)

- years 10+ 0.94 (0.79-1.12) 0.75* (0.62-0.90)

Breast cancer

mortality in:

- years 0-4 0.71 (0.62-0.80) (1.0)

- years 5-9 0.66 (0.58-0.75) 0.97 (0.79-1.18)

- years 10+

0.73 (0.62-0.86)

2p=0.0001

0.71 (0.58-0.88)

2p=0.0016 * 2p


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(n=10 645)

10 years tam. vs 5:ATLAS trial

(n=6846)

10 years tam. vs none:estimated effects

(product of two RRs)

Recurrence in:

- years 0-4 RR=0.53 (0.48-0.57) (1.0) RR=0.53 (0.48-0.57)

- years 5-9 0.68 (0.60-0.78) 0.90 (0.79-1.02) 0.61 (0.51-0.73)

- years 10+ 0.94 (0.79-1.12) 0.75* (0.62-0.90) 0.70* (0.54-0.91)

Breast cancer

mortality in:

- years 0-4 0.71 (0.62-0.80) (1.0) 0.71 (0.62-0.81)

- years 5-9 0.66 (0.58-0.75) 0.97 (0.79-1.18) 0.64 (0.50-0.82)

- years 10+

0.73 (0.62-0.86)

2p=0.0001

0.71 (0.58-0.88)

2p=0.0016

0.52 (0.40-0.68)

* 2p

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