Steven J. Chmura, MD, PhD, Compares Addition of Metastases-Directed Therapy vs SOC Alone for Oligometastatic Breast Cancer

Steven J. Chmura, MD, PhD, professor of radiation and cellular oncology, director of Clinical and Translational Research for Radiation Oncology, and Scientific Director of Cancer Clinical Trials at the University of Chicago Medicine

Prevailing treatment strategies for oligometastatic breast cancer involve stereotactic body radiotherapy or surgical resection plus standard of care (SOC) systemic therapy based on prior data suggesting progression-free survival (PFS) and overall survival (OS) benefit, but truly randomized studies examining these methods are lacking.

Steven J. Chmura, MD, PhD, professor of radiation and cellular oncology, director of Clinical and Translational Research for Radiation Oncology, and Scientific Director of Cancer Clinical Trials at the University of Chicago Medicine, recently presented data from the phase 2R/3 NRG-BR002 trial (NCT02364557) that tested metastases-directed therapy (MDT) plus systemic therapy vs systemic therapy alone in patients with newly diagnosed oligometastatic breast cancer at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Results of the trial showed no benefit to the addition of MDT, with a median PFS of 23 months (70% CI, 18-29) vs 19.5 months (70% CI, 17-36), respectively (HR, 0.92; 70% CI, 0.71-1.17; 1-sided log-rank P = .36).

In an interview with CancerNetwork^®, Chmura spoke about how results of the trial should influence his colleagues to consider different treatment options before subjecting their patients to potentially inefficacious treatment.

Q: What was the rationale for this research?

A: The overarching idea here is that we should view metastatic disease as a continuum, as something that can present on the one end as being quite widespread but on the other end as something with few areas and probably slow progression. If that continuum exists, then could we be intervening early in that cascade? Could we stop things in their tracks? The idea then is that if you intervene, [you may be able to] improve things like PFS and OS.

Q: What were the key findings of this research that stood out?

A: Prior to this study, there were innumerable single-institution, single-arm studies that showed great promise. Women who had limited spread of oligometastases, if they were treated aggressively, lived a long time and did quite well. [Different treatments were] never randomized in a true fashion to control for that. The outcome [of this study] shows why we have to [rely on] science. Talking about real-world data is fine, but it doesn’t tell us anything because those same real-world data had [everyone] assuming this worked. The bottom line is that it doesn’t work. It’s true that patients who present with a limited spread of disease do very well; systemic therapies work extremely well, and survival is fantastic. But it has nothing to do with the actual local intervention.

Q: How can these data be geared towards multidisciplinary practices?

A: If you do surveys and you look at the practice pattern—insurance even pays for these high-tech procedures to be done in first-line [setting]—in metastatic breast cancer, it has big implications. It should be stopped outside of clinical trials because any extra intervention you [perform] adds not only cost but a true potential for harm. I would hope this sort of routine practice, which has become quite common, comes to an end.

Q: How will this research potentially impact the treatment paradigm for this patient population?

A: Around 70% to 80% of patients are offered [systemic therapy plus local intervention] and they shouldn’t be. It should stop. The question is going to be whether there are competing forces to keep it going. It’ll be a question of how quickly it does stop and when. I don’t think that’s to say there may be populations this could help. Doing more studies is needed. If a woman has a very limited spread and they’re HER2 positive, if you just view them as one big group, adding this very expensive and potentially toxic therapy on top isn’t going to do any good.

Q: What do you hope your colleagues took away from this presentation?

A: The study was incredibly well done. The patients, staff, and everybody involved really put their bias aside and got it done. I think it became hard to even accrue patients because everybody assumed [the prevailing standard treatment strategy] would work. Anytime you randomized somebody to [a study arm in which they are not receiving] treatment, it’s hard to sell that. I hope they take away the quality of it and how definitively negative the results were. There’s no room for thinking maybe it works here or there. It just does not work.

Reference

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