Results of NRG-BR002 Trial Point to Need for Additional Research of Local Therapy for Oligometastatic Breast Cancer

Total ablation of all metastases in addition to standard systemic therapy did not improve progression-free survival (PFS) or overall survival (OS) compared with standard systemic therapy alone in patients with oligometastatic breast cancer, according to results from the phase 2R/3 NRG-BR002 trial (NCT02364557).¹

The trial evaluated patients with oligometastatic breast cancer with controlled locoregional disease and no more than 4 metastases who received no more than 12 months of systemic therapy without disease progression. All metastases needed to be amenable to stereotactic body radiation therapy, and the maximum diameter of any metastasis was 5 cm.

Patients were stratified by number of metastases, hormone receptor status, HER2 status, and receipt of prior chemotherapy for metastatic breast cancer. Patients were randomly assigned in a 1:1 fashion to symptom-directed palliative therapy plus standard systemic therapy vs total ablation of all metastases plus systemic therapy.

Those in the total ablation arm experienced a median PFS of 19.5 months compared with 23 months for systemic therapy alone. Additionally, the estimated 36-month OS was 68.9% (95% CI, 55.1%-82.6%) for ablation plus systemic therapy compared with 71.8% (95% CI, 58.9%-84.7%) for systemic therapy alone.

Although NRG-BR002 was a negative study, investigators have shown that prospective trials for patients with oligometastatic breast cancer can be conducted, according to Steven J. Chmura, MD, PhD, who added that more research is needed in this area.

“There has been so much written about [local therapy for oligometastatic breast cancer] and so much promise, and I believe there is plenty of room to do other clinical trials to investigate other areas, [such as] in the HER2[-positive] population or in patients who initially present with metastatic disease,” said Steven J. Chmura, MD, PhD, who presented on the management of oligometastatic breast cancer and the implications of the NRG-BR002 trial at the 40th Annual Miami Breast Cancer Conference^®.²

In an interview with OncLive^®, Chmura detailed his presentation on the management of oligometastatic breast cancer and key data from the NRG-BR002 trial, and expanded on the direction for future research in this patient population. Chmura is a professor of radiation and cellular oncology and a professor of medicine at the University of Chicago, as well as the Medical Director and Comprehensive Cancer Center director for Clinical and Translational Research for Radiation Oncology at UChicago Medicine, in Chicago, Illinois.

OncLive^®: How has the management of oligometastatic breast cancer evolved over time?

Chmura: It has now been more than 25 years since the [initiation of the conversation on] whether patients who have limited metastatic disease can receive types of local therapy, such as radiation or surgery, to improve overall outcomes in terms of PFS and OS.

In 25 years, a lot has been said about this [topic]. [Local therapy for oligometastatic disease] is commonly done based on single-institution [studies] and retrospective data. The entire point of NRG-BR002 was to design a good phase 3 trial to test if this intervention helps. It was exciting at the time because this was the first trial to test the hypothesis [of whether] local intervention could help.

We have acquired a lot of data [over the years], we have a lot of the publications, and we have a lot of hopes. However, what can we actually say that we can do in 2023? What impact does local therapy actually have [for oligometastatic disease]? How do the results of the NRG-BR002 trial, which was a negative trial, inform us going forward? Is there a path to go forward in terms of these local interventions?

Although NRG-BR002 was a negative trial, how has it helped inform practice now, and what could it mean for the future?

It is important to point out that the trial was in first-line, metastatic disease. It was [conducted in patients who were] almost entirely estrogen receptor/progesterone receptor–positive and HER2-negative who had small volume disease. Interestingly, this is the exact population of patients who all of the retrospective studies suggested could be helped [with local therapy].

Ultimately, [local] intervention failed to improve either OS or PFS . Therefore, I would hope that people look at this well-stratified, well-conducted trial and take home that off-protocol use of these local therapies, which could have significant toxicity, should probably stop.

How else can the treatment of oligometastatic disease be investigated?

[Trials in other patient populations] are being worked on now. The trial that we conducted answered the question about how the majority of people [have been treating oligometastatic breast cancer]. We now know to not do that, but future trials are going to ask more specific questions.

How would you approach treatment for a patient with oligometastatic disease right now?

If there is a patient who has a solitary metastasis, which is not causing a problem in terms of pain and compression, or does not represent an impending problem, we should probably not use local therapy; [rather], we should move forward with systemic options.

References

• Chmura SJ, Winter KA, Woodward WA, et al. NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). J Clin Oncol. 2022;40(suppl 16):1007. doi:10.1200/JCO.2022.40.16_suppl.1007
• Chmura SJ. Management of oligometastatic breast cancer: implications of NRG BR002. Presented at: 40th Annual Miami Breast Cancer Conference®; March 2-5, 2023; Miami Beach, FL.