Multicenter phase 2-3 trial of metastasis-directed ablation with first-line systemic therapy for oligometastatic breast cancer

Metastasis-directed therapy is increasingly used for metastatic breast cancer, despite its uncertain benefit during first-line systemic therapy. The multicenter phase 2-3 NRG-BR002 trial in the US and Canada evaluated whether metastasis-directed ablation improved progression-free survival (PFS) compared with first-line systemic therapy alone. Participant had ≤ 4 metastases, controlled primary disease, ≤ 12 months of first-line systemic therapy without progression, with all visible metastases amenable to SBRT or surgical resection. Participants were randomized 1:1 to systemic therapy alone or with metastasis-directed ablation. Primary endpoint was PFS. A total of 125 patients were eligible for analysis. Median age was 54 years, 79% had HR-positive, HER2-negative disease, 60% had solitary metastasi, 50% had bone involvement, and 37 bone only. With 72 PFS events and a median follow-up of 29.9 months, median PFS was 23.0 months in the no-ablation group and 19.5 months in the ablation group. Thus, the trial did not proceed to phase 3. OS did not differ significantly between groups. No grade 5 toxities occurred. Exploratory analysis suggested improved PFS with ablation among patients with low are absent pretreatment circulating tumor cells. The authors conclude that the addition of metastasis-directed ablation added to first-line systemic therapy did not improve PFS or OS among patients with oligometastatic breast cancer.