TOPLINE

Adding metastasis-directed ablation to first-line systemic therapy did not improve progression-free or overall survival in patients with oligometastatic breast cancer. Two-year overall survival estimates were 88.4% with systemic therapy alone and 78% with ablation.

METHODOLOGY

• Metastasis-directed therapy is increasingly being integrated into treatment for oligometastatic breast cancer, despite its uncertain benefit during first-line systemic therapy. 
• To investigate, the phase II/III NRG-BR002 trial enrolled 125 patients with oligometastatic breast cancer (≤4 metastases) across US and Canadian institutions. Most patients (60%) had solitary metastasis; 50% had bone involvement; and 37% had bone-only metastases.
• Patients were randomly assigned 1:1 to receive first-line systemic therapy alone or with metastasis-directed ablation using stereotactic body radiation therapy (SBRT) or surgery. Most patients in the ablation arm received SBRT (93%), with protocol-specified radiation doses administered within 6 weeks of study entry.
• The primary endpoint was progression-free survival, defined as time to progression or death, with secondary endpoints including overall survival and toxicity.

TAKEAWAY

• At a median follow-up of 29.9 months, with 72 events, median progression-free survival was 23 months with systemic therapy alone vs 19.5 months with ablation (hazard ratio [HR] 0.92; P = .36). With no signal of benefit from the addition of ablation, the trial did not progress to phase 3.
• During an extended follow-up (median, 57.5 months), median progression-free survival was 23 months with no ablation vs 29.5 months with ablation [HR, 0.93; P = .38).
• Overall survival did not differ significantly between arms (HR, 0.94; P = .41). At 2 years, overall survival estimates were 88.4% with systemic therapy alone vs 78% with ablation.
• Exploratory analysis suggested that patients with low or absent pretreatment circulating tumor cells (CTCs) had improved progression-free survival with ablation (interaction P = .029), while those with elevated CTCs did not benefit.

IN PRACTICE

“For now, metastasis-directed ablation with SBRT 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 study authors wrote. The approach, they added, “should be reserved for palliation of symptoms when needed or performed on clinical trials.”

SOURCE

The study was led by Steven J. Chmura, MD, PhD, of MD Anderson Cancer Center in Houston. It was published online in the Journal of Clinical Oncology.

LIMITATIONS

Most patients had HR‑positive, HER2-negative disease, limiting generalizability to other patient populations. More patients had relapsed (78%) vs de novo (22%) oligometastatic cancer, and the two may be distinct disease states warranting separate investigation. Systemic therapy administered before or after enrollment was not controlled, and time off systemic therapy to complete ablation varied.

DISCLOSURES

The study was supported by the National Cancer Institute, the Ludwig Foundation for Cancer Research, and the Breast Cancer Research Foundation. Multiple authors reported consulting fees, honoraria, research support, or stock ownership from various pharmaceutical and medical device companies, including Varian Medical Systems, AstraZeneca, Merck, and others. Full disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.