SUPREMO / BIG 2-04 MRC Trial

Design - Phase 3 international RCT: post-mastectomy chest wall irradiation (CWI) vs no CWI, intermediate-risk early breast cancer (NCT00966888 / ISRCTN61145589), N=1,607; primary 10-year overall survival.

OS at 10 years (primary, NEGATIVE) - 81.4% (CWI) vs 82.0% (no CWI); HR 1.04 (95% CI 0.82-1.30) - no survival benefit from chest wall irradiation.

Chest wall recurrence - Few events (29 total: 9 CWI vs 20 no CWI); CWI HR 0.45 (0.20-0.99) but absolute reduction <2%, deemed clinically insignificant.

Safety - Radiotherapy safety well characterized; cardiac and lung RT exposure recorded per protocol.

Regulatory - Radiotherapy-strategy trial - no FDA drug approval; chest wall irradiation may be safely omitted in intermediate-risk disease.

Sponsor - MRC/NIHR; EORTC Breast Cancer Group (BIG 2-04).

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.

Overall Survival at 10 Years — Primary Endpoint

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.

Overall Survival (OS)

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.

Safety & Tolerability

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.

Clinical Implications

❌ 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).

What is the SUPREMO trial?

SUPREMO (BIG 2-04) is a Phase 3 international randomized trial (NCT00966888; ISRCTN61145589) that tested whether post-mastectomy chest wall irradiation improves outcomes in intermediate-risk early breast cancer (for example, 1-3 positive nodes, or node-negative disease with high-risk features). About 1,607 patients were randomized, and 10-year overall survival was the primary endpoint.

Did SUPREMO show a benefit from chest wall irradiation?

No. SUPREMO was negative for its primary endpoint. Ten-year overall survival was 81.4% with chest wall irradiation versus 82.0% without it (HR 1.04; 95% CI 0.82-1.30) - no survival difference - suggesting that chest wall irradiation may be safely omitted in this intermediate-risk group.

What about local (chest wall) recurrence?

Chest wall recurrence events were very few (29 total: 9 with irradiation versus 20 without). While the hazard ratio favored irradiation (HR 0.45; 95% CI 0.20-0.99), the absolute reduction was less than 2%, which the investigators judged clinically insignificant given the lack of any overall-survival benefit.

Is there a drug or FDA approval involved in SUPREMO?

No. SUPREMO is a radiotherapy-strategy trial with no drug and no FDA approval question. Its findings inform radiation oncology practice - specifically, when post-mastectomy chest wall irradiation can be omitted in intermediate-risk early breast cancer.

Which patients does SUPREMO apply to?

SUPREMO enrolled intermediate-risk early breast cancer after mastectomy - pT1-2 with 1-3 positive nodes (pN1), pT3N0, or pT2N0 with grade III and/or lymphovascular invasion. The results should not be extrapolated to higher-risk disease (for example, 4 or more positive nodes), where post-mastectomy radiotherapy remains standard.