Background
Randomized phase II/III, open-label, US/Canadian NRG Oncology trial. N=129 enrolled (125 eligible). Oligometastatic breast cancer (≤4 metastases, controlled primary, all lesions amenable to SBRT or resection) after ≤12 months of non-progressing first-line systemic therapy. 79% HR+/HER2-, 60% solitary metastasis, 50% bone involvement (37% bone only). Question: does adding metastasis-directed ablation to ongoing first-line systemic therapy improve PFS?
Results
Interventions and follow up: Arm A: Systemic therapy + metastasis-directed ablation (SBRT in 93%, otherwise surgical resection)
Arm B: Systemic therapy alone (no ablation)
Primary endpoint: PFS (time to progression or death)
mFollow up: 29.9 months (72 PFS events)
Results: PFS: median 19.5 mo (ablation) vs 23.0 mo (no ablation); HR 0.92 (95% CI 0.57–1.47; 70% CI 0.71–1.17); 1-sided P=.36, stratified P=.42 ➡️ did not proceed to phase III
OS: HR 1.07 (95% CI 0.60–1.89); 1-sided P=.41, stratified P=.52
Exploratory (CTC): suggestion of improved PFS with ablation in patients with low/absent pretreatment CTCs
Arm B: Systemic therapy alone (no ablation)
Primary endpoint: PFS (time to progression or death)
mFollow up: 29.9 months (72 PFS events)
Results: PFS: median 19.5 mo (ablation) vs 23.0 mo (no ablation); HR 0.92 (95% CI 0.57–1.47; 70% CI 0.71–1.17); 1-sided P=.36, stratified P=.42 ➡️ did not proceed to phase III
OS: HR 1.07 (95% CI 0.60–1.89); 1-sided P=.41, stratified P=.52
Exploratory (CTC): suggestion of improved PFS with ablation in patients with low/absent pretreatment CTCs
Adverse events
Grade 5: none
Other toxicity detail: NR in abstract
Other toxicity detail: NR in abstract
Conclusions
Adding metastasis-directed ablation to first-line systemic therapy did not improve PFS or OS in oligometastatic breast cancer. Ablation should not be used routinely outside clinical trials, except for palliation.
Key Limitations
Phase II/III design stopped at the phase II stage (not powered for definitive OS conclusion); only 72 PFS events and wide CIs (95% CI 0.57–1.47) cannot exclude a clinically meaningful benefit or harm. Open-label. Accrual 2014–2019 spanned the transition to CDK4/6 inhibitor-based first-line therapy, and the population was heterogeneous (bone-predominant, mixed subtypes, ≤12 months of prior systemic therapy). CTC findings are exploratory and hypothesis-generating.
Clinical Context
Negative randomized evidence against routine SBRT/surgical ablation of oligometastatic breast cancer on top of first-line systemic therapy, tempering enthusiasm from smaller randomized oligometastasis studies in mixed tumor types. Supports continuing systemic therapy as the backbone, with ablation reserved for palliation or clinical trials. No regulatory implications (radiation/surgical strategy).
