NRG-BR002: A Randomized Phase II/III Trial of Metastases-Directed Ablation with First-Line Systemic Therapy for Oligometastatic Breast Cancer
Abstract
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. Patients and 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 randomized 1:1 to systemic therapy alone(No-Ablation) or with metastasis-directed ablation(Ablation). The primary endpoint was PFS, defined as time to progression or death. Secondary endpoints included overall survival(OS) and toxicity. Circulating tumor cells(CTCs) were evaluated as exploratory biomarkers. Results: From December 2014-September 2019, 129 patients were enrolled; 125 eligible for analysis. Median age was 54 years; 79% hormone receptor–positive, HER2-negative disease, 60% solitary metastasis, 50% had bone involvement, 37% bone only. Ablation was delivered via SBRT for 93%. With 72 PFS events and median follow-up of 29.9 months, median PFS was 23.0 months(No-Ablation) vs 19.5 months(Ablation) (hazard ratio [HR] 0.92; 70% CI, 0.71–1.17; 95% CI, 0.57–1.47); 1-sided p=0.36; stratified p=0.42). Thus, the trial did not proceed to Phase III. OS did not differ significantly between arms (HR 1.07; 95% CI, 0.60–1.89; 1-sided p=0.41; stratified p=0.52). No grade 5 toxicities occurred. Exploratory analysis suggested improved PFS with ablation in patients with low or absent pretreatment CTCs. Conclusions: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02364557