SBRT Ablation Fails to Extend PFS in Oligometastatic Breast Cancer

Adding stereotactic body radiation therapy (SBRT) or surgery directed at every known metastasis to first-line systemic therapy did not improve progression-free survival (PFS) or overall survival (OS) in patients with oligometastatic breast cancer, according to results published in the Journal of Clinical Oncology.¹

In the randomized phase 2 portion of the phase 2/3 NRG-BR002 trial (NCT02364557), median PFS was 23.0 months with systemic therapy alone vs 19.5 months with the addition of metastasis-directed ablation (HR, 0.92; 95% CI, 0.57-1.47; 1-sided P =.36) at a median follow-up of 29.9 months. Because the result fell short of the prespecified signal needed to continue, the trial closed without advancing to phase 3. OS also did not differ significantly between the arms.

“This randomized trial gives us important evidence that, for most patients in this setting, adding local treatment to effective systemic therapy does not improve progression-free or overall survival,” said Steven J. Chmura, MD, PhD, chair of Breast Radiation Oncology at The University of Texas MD Anderson Cancer Center in Houston, in a news release.²

Study Design

Between December 2014 and September 2019, 129 patients were enrolled at 47 institutions in the United States and Canada, and 125 were evaluated in this analysis. Patients had 4 or fewer metastases, each no larger than 5 cm and amenable to SBRT or resection, a controlled primary tumor, and no progression during up to 12 months of first-line systemic therapy. Brain metastases and malignant pleural effusion were exclusion criteria.

Randomization was 1:1 between systemic therapy alone and systemic therapy plus ablation of all metastases, with a systemic regimen selected by physician’s choice. The phase 2 portion was powered to detect an HR of 0.55, corresponding to an increase in median PFS from 10.5 to 19 months, at a 1-sided P-value of .15.

The median age was 54 years. Most patients (79%) had hormone receptor-positive, HER2-negative disease, whereas 60% had a single metastasis, 50% had bone involvement, and 37% had bone-only disease. Relapsed disease accounted for 78% of cases and 22% had de novo stage IV disease. In the ablation arm, 56 patients (93%) received SBRT and 1 underwent resection.

Key Results and Extended Follow-Up

At the go/no-go analysis with a median follow-up of 29.9 months, there were 72 PFS events, including 66 instances of progression and 6 deaths. Of these events, 42 were in the no-ablation arm and 30 in the ablation arm. Although only 20 of 60 patients (33%) in the ablation arm had progression in the ablated area, a further 10 had progression outside of the ablated area. Two-year estimated OS rates were 88.4% in the no-ablation arm and 78.0% for the ablation arm.

With extended follow-up to 57.5 months, no significant PFS difference was shown. Median PFS was 23.0 months without ablation and 29.5 months with ablation (HR, 0.93; 95% CI, 0.60-1.44; 1-sided P =.38), and 4-year PFS rates were 26.8% and 33.8%, respectively. With 56 deaths, 4-year OS was 63.4% without ablation vs 59.7% with ablation (HR, 0.94; 95% CI, 0.56-1.60; 1-sided P =.41).

Safety Findings

No grade 5 toxicities occurred in either arm. In the ablation arm, grade 3 toxicities were reported in 3 patients (5%) and no grade 4 events occurred. In the systemic therapy-alone arm, 7 patients had grade 3 toxicities and 1 had a grade 4 event.

Exploratory Circulating Tumor Cell Analysis

Of 108 patients who consented to blood collection, pretreatment circulating tumor cells (CTCs) were available for 62 by the CellSearch assay and for 60 by the High-Definition Single Cell Assay (HDSCA). Neither assay was prognostic for PFS in the overall population. However, PFS improved with ablation in patients with HDSCA counts below the first quartile (interaction P =.029) and in those with no CTCs detected by CellSearch (interaction P =.03). The institution stated that future trials will incorporate blood-based markers such as CTCs and circulating tumor DNA to select patients.

Clinical Implications

The authors concluded that, outside of clinical trials, ablation does not belong in routine first-line management of oligometastatic breast cancer and should be reserved for palliation of symptoms. They noted that most patients had hormone receptor-positive, HER2-negative disease, which limits application to triple-negative and HER2-positive breast cancer, that subgroups were small, and that systemic therapy before and after enrollment was not controlled.

“More treatment is not always better treatment,” Chmura said in the news release.

REFERENCES

1. Chmura SJ, Winter KA, Woodward WA, et al. NRG-BR002: a randomized phase II/III trial of metastasis-directed ablation with first-line systemic therapy for oligometastatic breast cancer. J Clin Oncol. Published online October 7, 2026. doi:10.1200/JCO-26-00201

2. Randomized trial finds targeting individual metastases in oligometastatic breast cancer does not improve survival. News release. The University of Texas MD Anderson Cancer Center. October 7, 2026. Accessed October 9, 2026. https://tinyurl.com/z7w53cbe