NRG-BR002: Metastasis-directed ablation (SBRT/surgery) fails to extend PFS in oligometastatic breast cancer on 1L systemic therapy

NRG-BR002 tested metastasis-directed ablation (93% SBRT; remainder surgical resection)—a local control strategy intended to eradicate visible metastatic deposits—added to first-line systemic therapy in oligometastatic breast cancer (≤4 metastases) with controlled primary disease and no progression after ≤12 months of 1L systemic therapy. In this randomized Phase II/III US/Canada trial (NCT02364557), 125 eligible patients (median age 54; 79% HR+/HER2−; 60% solitary metastasis; 50% bone involvement; 37% bone-only) were randomized 1:1 to systemic therapy alone vs systemic therapy + ablation; median PFS was 23.0 vs 19.5 months (HR 0.92; 95% CI 0.57–1.47; 1-sided p=0.36), with no OS difference (HR 1.07; 95% CI 0.60–1.89). The trial did not proceed to its planned Phase 3 portion after failing the prespecified Phase 2 efficacy threshold. In a non-prespecified extended follow-up analysis, median PFS was 23.0 months without ablation versus 29.5 months with ablation (HR 0.93), still without a significant difference. Thus, neither the initial nor longer-term analysis demonstrated an overall benefit from adding metastasis-directed treatment. No grade 5 toxicities were seen; an exploratory signal suggested better PFS with ablation in patients with low/absent baseline circulating tumor cells (CTCs)—noting CTC burden is a known prognostic marker in metastatic breast cancer, often using a ≥5 CTCs/7.5 mL threshold on CellSearch.