NRG-BR002: A Randomized Phase II/III Trial of Metastasis-Directed Ablation With First-Line Systemic Therapy for Oligometastatic Breast Cancer
Mené sur 125 patientes atteintes d'un cancer du sein oligométastatique (âge médian : 54 ans ; durée médiane de suivi : 29,9 mois), cet essai randomisé international de phase III évalue l'intérêt, du point de vue de la survie sans progression, d'ajouter une ablation ciblée des métastases au traitement systémique de première ligne
PURPOSE: Metastasis-directed therapy is increasingly used for oligometastatic breast cancer, despite its uncertain benefit during first-line systemic therapy. We evaluated whether metastasis-directed ablation improves progression-free survival (PFS) compared with first-line systemic therapy alone in patients with oligometastatic breast cancer.
METHODS: NRG-BR002 is a randomized phase II/III trial across US/Canadian institutions. Participants had ≤4 metastases, controlled primary disease, ≤12 months of first-line systemic therapy without progression with all visible metastases amenable to stereotactic body radiation therapy (SBRT) or surgical resection and were randomly assigned 1:1 to systemic therapy alone (no ablation) or with metastasis-directed ablation (ablation). The primary end point was PFS, defined as time to progression or death. Secondary end points included overall survival (OS) and toxicity. Circulating tumor cells (CTCs) were evaluated as exploratory biomarkers.
RESULTS: From December 2014 to September 2019, 129 patients were enrolled; 125 were eligible for analysis. Median age was 54 years; 79% had hormone receptor–positive, human epidermal growth factor receptor 2‑negative disease, 60% solitary metastasis, 50% bone involvement, and 37% bone only. Ablation was delivered via SBRT for 93%. With 72 PFS events and a median follow-up of 29.9 months, median PFS was 23.0 months (no ablation) versus 19.5 months (ablation; hazard ratio [HR], 0.92 [70% CI, 0.71 to 1.17; 95% CI, 0.57 to 1.47]; one-sided P = .36; stratified P = .42). Thus, the trial did not proceed to phase III. OS did not differ significantly between arms (HR, 1.07 [95% CI, 0.60 to 1.89]; one-sided P = .41; stratified P = .52). No grade 5 toxicities occurred. Exploratory analysis suggested improved PFS with ablation in patients with low or absent pretreatment CTCs.
CONCLUSION: The addition of metastasis-directed ablation added to first-line systemic therapy did not improve PFS or OS in patients with oligometastatic breast cancer. Ablation should not be routinely used outside of clinical trials, except for palliation. Line graph comparing progression-free survival with and without ablation for breast cancer.Line graph comparing progression-free survival with and without ablation for breast cancer.Line graph comparing progression-free survival with and without ablation for breast cancer.Line graph comparing progression-free survival with and without ablation for breast cancer.
Journal of Clinical Oncology , résumé, 2026