NRG-BR002 trial finds ablation does not improve survival in oligometastatic breast cancer

The randomized phase II/III NRG-BR002 trial, led by Dr. Steven J. Chmura of the MD Anderson Cancer Center, has found that adding metastasis-directed ablation to first-line systemic therapy does not improve progression-free or overall survival for patients with oligometastatic breast cancer. The trial, which evaluated 125 eligible patients, showed no significant survival differences, prompting researchers to recommend against routine use of local radiation or surgery in this setting to spare patients unnecessary toxicity and healthcare costs.

Survival and progression outcomes

• ▪The NRG-BR002 trial did not progress to a phase III study because adding metastasis-directed ablation failed to show a signal of benefit or the required improvement in progression-free survival.
• ▪Overall survival did not differ significantly between the treatment arms, with two-year overall survival estimates at 88.4% with systemic therapy alone compared to 78% with the addition of ablation.
• ▪The NRG-BR002 trial found that treating all visible metastases with radiation or surgery did not prevent new metastases from developing elsewhere in patients with oligometastatic breast cancer.
• ▪At median follow-ups of 29.9 and 57.5 months, median progression-free survival was 23 months with systemic therapy alone compared to 19.5 and a statistically similar 29.5 months with metastasis-directed ablation.

Recommendations against routine ablation

• ▪The NRG-BR002 study authors concluded that metastasis-directed ablation should not be routinely used with first-line systemic therapy for oligometastatic breast cancer, but should be reserved for symptom palliation or clinical trials.
• ▪Steven J. Chmura stated that avoiding routine local ablation can spare oligometastatic breast cancer patients from additional treatments that add time, healthcare costs, and potential side effects without improving survival.

Role of blood-based biomarkers

• ▪Future clinical trials led by Chelain Goodman plan to incorporate blood-based markers, such as circulating tumor cells and circulating tumor DNA, to better identify which oligometastatic breast cancer patients might benefit from targeted treatment.
• ▪An exploratory analysis led by Wendy A. Woodward suggested that patients with low or absent pretreatment circulating tumor cells (CTCs) had improved progression-free survival with ablation, while those with elevated CTCs did not benefit.

Patient population and characteristics

• ▪The phase II/III NRG-BR002 clinical trial evaluated 125 eligible patients with oligometastatic breast cancer across 47 U.S. and Canadian institutions to test the efficacy of adding metastasis-directed ablation to first-line systemic therapy.
• ▪Among the patients enrolled in the NRG-BR002 trial, 60% had a solitary metastasis, 50% had bone involvement, and 37% had bone-only metastases.
• ▪Oligometastatic breast cancer refers to metastatic disease that has spread beyond the original tumor but remains confined to a small number of sites, defined in the NRG-BR002 trial as four or fewer metastases.

Debatable claims

• ▪Pretreatment circulating tumor cell levels are a reliable basis for selecting breast cancer patients for ablation
• ▪Metastasis-directed ablation should be reserved for symptom palliation in oligometastatic breast cancer
• ▪Simply counting visible metastases is sufficient to define oligometastatic breast cancer for treatment purposes