Intermediate-risk early breast cancer post-mastectomy (pT1-2 N1; pT3N0; or pT2N0 grade III and/or LVI) — Medical Research Council (MRC) / NIHR partnership; EORTC Breast Cancer Group; Dutch Cancer Society; Cancer Australia; HSBC Trustees; Breast Cancer Institute of Edinburgh; Edinburgh Cancer Centre Endowments; University of Edinburgh
Intermediate-risk early breast cancer post-mastectomy (pT1-2 N1; pT3N0; or pT2N0 grade III and/or LVI)SABCS 2024 GS2-03
[Slide 1]
BREAST CANCER
RESULTS: Overall Survival
SYMPOSIUM
UT Health
AACR
to
Overall Survival by Randomized Treatment and NO or N+ Status
NO Patients
N+ Patients
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
1.00
1.00
Survival probability
0.75
0.50
0.25
Survival probability
0.75
0.50
Log-rank P = 0.40
0.25
Log-rank P = 0.90
HR 1.21 (95% Cl: 0.79. 1.85)
HR 0.97 (95% CI: 0.74, 1.28)
0.00
0.00
0
5
10
0
5
10
Time (years)
Time (years)
Number at risk
Number at risk
Trial arm
211
177
58
Trial arm
587
518
147
191
160
48
614
528
143
0
5
10
0
5
10
Time (years)
Time (years)
---
[Slide 2]
SAN ANTONIO
BREAST CANCER
RESULTS: Regional Recurrence
SYMPOSIUM
UT Health
AACR
-
I
I
Regional Recurrence by Randomized Treatment and NO or N+ Status
NO Patients
N+ Patients
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
1.00
1.00
Survival probability
0.75
0.50
Log-rank P - 1.0
Servival probability
0.75
0.50
0.25
0.25
Log-rank P - 0.03
HR 1.00 (95% Cl: 0.36, 2.77)
HR 0.51 (95% Cl: 0.27. 0.96)
0.00
0.00
0
5
10
0
5
10
Time (years)
Time (years)
Number at risk
Number at risk
Trial arm
211
173
58
Trial arm
587
509
146
191
160
50
614
524
142
0
5
10
0
5
10
Time (years)
Time (years)
---
[Slide 3]
BREAST CANCER
SYMPOSIUM
RESULTS: Metastasis-free & Disease-free Survival
UT Health AACR
-
December 10-13, 2024
Kaplan-Meier Curves for ITT Population:
Kaplan-Meier Curves for ITT Population:
Metastasis-free Survival by Randomized Treatment
Disease-free Survival by Randomized Treatment
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
1.00
1.00
Survival probability
0.75
0.50
Survival probability
0.75
0.50
0.25
Log-rank D = 0.60
No CWI events = 166 (20.8%)
0.25
Log-rank p = 70
No CWI events = 196 (24.5%)
HR 1.06 (95% CI: 0.86, 1.31)
CWI events - 176 (21.8%)
HR 0.97 (95% CI: 0.79. 1.18)
CWI events - 192 (23.8%)
0.00
0.00
0
5
10
0
5
10
Time (years)
Time (years)
Number at risk
Number at risk
Trial arm
799
668
199
Trial arm
799
648
192
808
668
185
808
659
180
0
5
10
0
5
10
Time (years)
Time (years)
This presentation is the intellectual property of the author/prenerner Contact them - nt for perminare to reprint and/or distribute
---
[Slide 4]
SAN ANTONIO
BREAST CANCER
CONCLUSIONS
SYMPOSIUM
UT Health AACR
-
Internal
- -
December 10-13, 2024
In patients with 1-3 positive nodes or pN0 with other risk factors adjuvant chest
wall irradiation with optimal systemic therapy:
(a) Does not improve 10 year overall survival
(b) Results in a clinically insignificant reduction in 10 year chest wall recurrence (< 2%)
(c) Has no impact on disease free or metastasis free survival
(d) Incremental improvements in multidisciplinary care probably explain the
results
(e) Adjuvant chest wall irradiation should be omitted in most patients meeting
eligibility criteria for SUPREMO
This presentation is the intellectual property of the author/presentes Contact them if ed acade for permission to reprint and/or distribute.
[Slide 1]
SAN ANTONIO
BREAST CANCER
CONCLUSIONS
SYMPOSIUM
UT Health AACR
-
I
-
-
December 10-13, 2024
In patients with 1-3 positive nodes or pNO with other risk factors adjuvant chest
wall irradiation with optimal systemic therapy:
(a) Does not improve 10 year overall survival
(b) Results in a clinically insignificant reduction in 10 year chest wall recurrence (< 2%)
(c) Has no impact on disease free or metastasis free survival
(d) Incremental improvements in multidisciplinary care probably explain the
results
(e) Adjuvant chest wall irradiation should be omitted in most patients meeting
eligibility criteria for SUPREMO
This presentation is the Intellectual property of the author/presenter. Contact them at v1ikunki@exseed.ed.ac.uk for permission to reprint and/or distribute.
[Slide 1]
SAN ANTONIO
CONCLUSIONS
BREAST CANCER
SYMPOSIUM
UT Health
AACR
-
December 10-13, 2024
In patients with 1-3 positive nodes or pNO with other risk factors adjuvant chest
wall irradiation with optimal systemic therapy:
(a) Does not improve 10 year overall survival
(b) Results in a clinically insignificant reduction in 10 year chest wall recurrence (< 2%)
(c) Has no impact on disease free or metastasis free survival
(d) Incremental improvements in multidisciplinary care probably explain the
results
(e) Adjuvant chest wall irradiation should be omitted in most patients meeting
eligibility criteria for SUPREMO
This presentation is the intellectual property of the author/presenter. Contact them at v1ikunkl@exseed.ed.ac.uk for permission to reprint and/or distribute.
---
[Slide 2]
SAN ANTONIO
RESULTS: Overall Survival
BREAST CANCER
SYMPOSIUM
UT Health
AACR
before
Rej Case Center
Kaplan-Meier Curves for ITT Population: Overall Survival by Randomized Treatment
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
1.00
0.75
0.50
0.25
Log-rank p = 0.79
No CWI deaths = 145 (18.1%)
HR 1.04 (95% CI: 0.82, 1.30)
CWI deaths = 150 (18.6%)
0.00
0
5
10
Time (years)
Number at risk
799
695
205
808
689
191
0
5
10
Time (years)
---
[Slide 3]
SAN ANTONIO
BREAST CANCER
RESULTS: Chest Wall Recurrence
SYMPOSIUM?
UT Health
AACR
Kaplan-Meier Curves for ITT Population: Local Recurrence by Randomized Treatment
Trial arm
-
No Chest Wall Irradiation
Chest Wall Irradiation
1.00
Trial arm - No Chest Wall Irradiation - Chest Wall Irradiation
0.75
NNT = 62.5
1,000
95% CI: (33.3, 500.0)
0.975
0.50
0.950
0.25
0.925
Log-rank p = 0.04
CWI events = 9 (1.1%)
HR 0.45 (95% CI: 0.20, 0.99)
No CWI events = 20 (2.5%)
0.900
0
5
10
0.00
Time (years)
0
5
10
Time (years)
Number at risk
799
691
205
808
690
194
0
5
10
Time (years)
---
[Slide 4]
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
DECEMBER 10-13, 2024
AAGR
HENRY a. GONZALE CONVENTION CENTER SAN ANTONIO, TX
UT Health
Does postmastectomy radiotherapy in 'intermediate-risk' breast cancer
impact overall survival? 10 year results of the BIG 2-04 MRC randomized
trial on behalf of the SUPREMO trial investigators
lan Kunkler, FRCR
Institute of Genetics and Cancer
University of Edinburgh
Medical
Research
MRC
Council
11/11
---
[Slide 5]
SAN ANTONIO
BREAST CANCER
RESULTS: Overall Survival
SYMPOSIUM*
UT Health
AAGR
-
-
-
I I I
Kaplan-Meier Curves for ITT Population: Overall Survival by Randomized Treatment
Trial arm
No Chest Wall Irradiation
+
Chest Wall Irradiation
1.00
Survival probability
0.75
0.50
0.25
Log-rank p = 0.79
No CWI deaths = 145 (18.1%)
HR 1.04 (95% Cl: 0.82, 1.30)
CWI deaths = 150 (18.6%)
0.00
0
5
10
Time (years)
Number at risk
Trial arm
799
695
205
808
689
191
0
5
10
Time (years)
---
[Slide 6]
SAN ANTONIO
BREAST CANCER
RESULTS: Chest Wall Recurrence
SYMPOSIUM*
UT Health
AACR
I
-
- -
I I
Kaplan-Meier Curves for ITT Population: Local Recurrence by Randomized Treatment
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
1.00
Trial arm
No Chest Wall Irradiation
Chest Wall Irradiation
NNT = 62.5
1.000
Survival probability
0.75
95% Cl: (33.3, 500.0)
Survival probability
0.975
0.50
0.950
0.925
0.25
Log-rank p = 0.04
CWI events = 9 (1.1%)
HR 0.45 (95% Cl: 0.20, 0.99)
No CWI events = 20 (2.5%)
0.900
0
5
10
0.00
Time (years)
0
5
10
Time (years)
Number at risk
Trial arm
799
691
205
808
690
194
0
5
10
Time (years)
---
[Slide 7]
SAN ANTONIO
BREAST CANCER
CONCLUSIONS
SYMPOSIUM*
UT Health AACR
-
Market
I I I
- -
December 10-13, 2024
In patients with 1-3 positive nodes or pN0 with other risk factors adjuvant chest
wall irradiation with optimal systemic therapy:
(a) Does not improve 10 year overall survival
(b) Results in a clinically insignificant reduction in 10 year chest wall recurrence (< 2%)
(c) Has no impact on disease free or metastasis free survival
(d) Incremental improvements in multidisciplinary care probably explain the
results
(e) Adjuvant chest wall irradiation should be omitted in most patients meeting
eligibility criteria for SUPREMO
This presentation is the intellectual property of the author/presenter. Contact them at v1ikunkl@exsed.ed.ac.uk for permission to reprint and/or distribute.
[Slide 1]
SAN ANTONIO
BREAST CANCER
CONCLUSIONS
SYMPOSIUM
UT Health
AAGR
-
- -
-
December 10-13, 2024
In patients with 1-3 positive nodes or pNO with other risk factors adjuvant chest
wall irradiation with optimal systemic therapy:
(a) Does not improve 10 year overall survival
(b) Results in a clinically insignificant reduction in 10 year chest wall recurrence (< 2%)
(c) Has no impact on disease free or metastasis free survival
(d) Incremental improvements in multidisciplinary care probably explain the
results
(e) Adjuvant chest wall irradiation should be omitted in most patients meeting
eligibility criteria for SUPREMO
This proventation b Do interfection property of the Contact Non d United adadas - perovasion to reprint tritter distribute
---
[Slide 2]
SAN ANTONIO
BREAST CANCER
RESULTS: Overall Survival
SYMPOSIUM"
UT Health
AAGR
-
- - -
Tax Cana Charge
Kaplan-Meler Curves for ITT Population: Overall Survival by Randomized Treatment
Trial arm
+
No Chest Wall Irradiation
Chest Wall Imediation
1.00
Survival probability
0.75
0.50
0.25
Log-rank P = 0.79
No CWI deaths = 145 (18.1%)
HR 1.04 (95% Cl: 0.82, 1.30)
CWI deaths = 150 (18.6%)
0.00
0
5
10
Time (years)
Number at risk
Trial arm
799
695
205
808
680
191
0
5
10
Time (years)
---
[Slide 3]
Main eligibility criteria
SAN ANTONIO
BREAST CANCER
SYMPOSIUM
UT Isalth
AAGR
-
- -
-
-
December 10-13, 2024
pT1N1M0;pT2N1M0 or pT3NOMO histologically confirmed invasive breast cancer.
pT2N0M0 if grade 3 and/or lymphovascular invasion
Undergone simple mastectomy (with minimum of 1mm clear margin) and an axillary staging
procedure
If axillary node clearance node positive (1-3 positive nodes) then an axillary node clearance
(minimum of 8 nodes removed) should have been performed.
Axillary node negative status can be determined on the basis of either axillary node clearance, or
axillary node sampling or sentinel node biopsy
Fit for adjuvant or neoadjuvant chemotherapy (if indicated), adjuvant endocrine therapy (if
indicated) and postoperative irradiation.
Written informed consent
www.supremo-trial.com
this prevention b (he interved property of the Condect Dear a od and for permission to reprint Getributz
SUPREMO is the definitive Phase 3 trial evaluating whether post-mastectomy chest wall irradiation (CWI) is needed for intermediate-risk breast cancer (1-3 positive nodes, or node-negative with high-risk features like grade 3 / LVI). At 9.6 years median follow-up, NO survival benefit from CWI (81.4% vs. 82.0% 10-yr OS, HR 1.04). Although CWI reduced chest wall recurrence risk by half, the absolute benefit was <2% — clinically insignificant. Results important for shared decision-making: many eligible patients may safely AVOID CWI. Reinforces the movement to minimize radiation exposure in intermediate-risk BC, complementing PRIME II (RT omission in 65+), CALGB 9343 (70+), and IDEA (RT omission by genomic risk).
Median: 81.4 % 10-year OS (chest wall irradiation (CWI)) vs. 82.0 % 10-year OS (no CWI). HR 1.04 (95% CI 0.82-1.30) 10-year OS rate: 81.4% (CWI) vs. 82.0% (no CWI). Median follow-up (years) rate: 9.6% (years). Phase 3 international RCT (ISRCTN61145589). N=1,607 randomized (CWI 808, no CWI 799) between April 2006 and April 2013. Population: intermediate-risk post-mastectomy BC — pT1-2 N1; pT3N0; or pT2N0 grade III and/or LVI. CWI: 50 Gy/25 fx or 40 Gy/15 fx equivalent. Median follow-up 9.6 years. Primary endpoint 10-year OS: 81.4% (CWI) vs. 82.0% (no CWI), HR 1.04 (95% CI 0.82-1.30) — NO difference. Endpoint NOT MET. No survival benefit from CWI in this population. Kunkler et al., SABCS 2024 GS2-03.
❌ 10-yr OS 81.4% CWI vs 82.0% no CWI (HR 1.04, not significant)
HR 1.04 (95% CI 0.82-1.30) Primary 10-year OS endpoint not met (see above). Secondary: chest wall recurrence events only 29 total (9 CWI, 20 no CWI); CWI HR 0.45 (95% CI 0.20-0.99), but absolute rate reduction <2% — investigator deemed clinically insignificant. 98.8% vs. 97.1% chest wall recurrence-free survival. No differential treatment effect in pN1 vs. pN0 (P for interaction = 0.13). Limitations: low accrual of pT3N0 disease, better-than-anticipated overall survival.
Radiotherapy safety well-characterized. Specific CWI acute/late toxicity endpoints (skin reactions, pneumonitis, cardiac events, secondary malignancy) not emphasized in primary results — focus was OS. Cardiac and lung RT exposure were recorded per protocol.
❌ Negative: Post-mastectomy CWI has no impact on 10-year OS in intermediate-risk BC. Omission may be safe. SUPREMO is the definitive Phase 3 trial evaluating whether post-mastectomy chest wall irradiation (CWI) is needed for intermediate-risk breast cancer (1-3 positive nodes, or node-negative with high-risk features like grade 3 / LVI). At 9.6 years median follow-up, NO survival benefit from CWI (81.4% vs. 82.0% 10-yr OS, HR 1.04). Although CWI reduced chest wall recurrence risk by half, the absolute benefit was <2% — clinically insignificant. Results important for shared decision-making: many eligible patients may safely AVOID CWI. Reinforces the movement to minimize radiation exposure in intermediate-risk BC, complementing PRIME II (RT omission in 65+), CALGB 9343 (70+), and IDEA (RT omission by genomic risk).
