The addition of metastasis-directed ablation to first-line systemic therapy did not significantly improve progression-free or overall survival in patients with oligometastatic breast cancer, according to findings from the randomized phase II portion of the NRG-BR002 trial reported by Chmura et al in the Journal of Clinical Oncology. Although ablation was generally well tolerated, the investigators concluded that the approach should not be routinely used outside clinical trials, except for palliation.
Study Details
NRG-BR002 was a randomized phase II/III trial conducted at 47 institutions in the United States and Canada. Between December 2014 and September 2019, 129 patients were enrolled, of whom 125 were eligible for analysis. Eligible patients had biopsy-proven oligometastatic breast cancer, defined as four or fewer metastases measuring ≤ 5 cm, controlled primary disease, and no progression during up to 12 months of first-line systemic therapy. All metastases had to be amenable to stereotactic body radiation therapy or surgical resection.
Patients were randomly assigned 1:1 to receive first-line systemic therapy alone (n = 65) or systemic therapy plus metastasis-directed ablation (n = 60). The primary endpoint was progression-free survival, with overall survival and toxicity assessed as secondary endpoints. Circulating tumor cells were evaluated as exploratory biomarkers.
The median patient age was 54 years; 79% had hormone receptor–positive, HER2-negative disease; 60% had a solitary metastasis; and 50% had bone involvement. Most patients (78%) had relapsed metastatic disease. Among patients assigned to ablation, 93% received stereotactic body radiation therapy.
Key Results
At the primary phase II analysis, after a median follow-up of 29.9 months, 72 progression-free survival events had occurred. Median progression-free survival was 23.0 months with systemic therapy alone vs 19.5 months with ablation (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = 0.57–1.47; one-sided P = .36). The corresponding 2-year progression-free survival rates were 45.7% and 46.8%, respectively. Because the trial did not demonstrate the prespecified signal of benefit, it did not proceed to phase III.
An extended analysis, conducted after a median follow-up of 57.5 months, confirmed the absence of a significant progression-free survival benefit. Median progression-free survival was 23.0 months without ablation vs 29.5 months with ablation (HR = 0.93, 95% CI = 0.60–1.44; one-sided P = .38). Overall survival also did not differ significantly between treatment groups (HR = 0.94, 95% CI = 0.56–1.60; one-sided P = .41). Four-year overall survival rates were 63.4% and 59.7%, respectively.
Treatment was generally well tolerated, with no grade 5 toxicities. Grade 3 toxicities occurred in seven patients receiving systemic therapy alone and three patients receiving ablation.
Exploratory analyses suggested that patients with absent or very low pretreatment circulating tumor cell levels might derive a progression-free survival benefit from ablation. Significant treatment interactions were observed using both circulating tumor cell assays (P = .030 and .029), although the investigators cautioned that subgroup sizes were small.
“For now, metastasis-directed ablation with [stereotactic body radiation therapy] or surgery with its attendant potential for patient toxicity as well increased health care costs should not be routinely used with first-line systemic therapy for the treatment of oligometastatic breast cancer. The use of metastases-directed therapy should be reserved for palliation of symptoms when needed or performed on clinical trials,” the authors concluded.
Steven J. Chmura, MD, PhD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Cancer Institute of the National Institutes of Health. For full disclosures of the study authors, visit ascopubs.org.
