Coordinated Care in Breast Oncology: Clinical Trials and De-escalation of Treatment

In this episode of OncChats: Coordinated Care in Breast Oncology, Jason Ye, MD, and Daphne B. Stewart, MD, of Keck Medicine of USC, discuss how coordinated clinical trial participation enables safer treatment de-escalation and advances breast cancer care through national research efforts.

Ye: I think that’s a good segue to talk about our clinical trial offerings. As you mentioned, there are a lot of trials [being done] in breast cancer. Because outcomes [are] so improved these days, [trials are examining ways to] de-escalate treatment and see whether we can [achieve an] equivalent outcome without putting patients through as much treatment. I think that is definitely a recurring theme in the radiation oncology field for some of the recent breast cancer trials.

I just want to mention a few that are exciting that we took part in at our institution, at USC. One of them is the NSABP B-51 trial [NCT01872975]. [This] looked into patients who had neoadjuvant chemotherapy; they initially had a lymph node in the axilla involved, but the lymph node cancer was completely wiped out by chemotherapy. [The question was,] can [we] perhaps decrease the field or amount of radiation? That trial showed some excellent early results, and so that is allowing us to gradually de-escalate the radiation. In some cases, patients may skip radiation altogether if they’re really favorable; we were definitely not doing that before a few years back. So, we’re starting [to consider] that.

Another one that I’m really happy about was the [phase 3] Alliance 221505 trial [NCT03414970]; there’s a charming acronym for it, called RT CHARM. That trial looks into [the question of,] for patients who have a mastectomy and need radiation, can we shorten the radiation from their standard 5-week, everyday radiation to only 3 weeks? The trial result was just presented a few months ago at our national meeting, and it was a great success. At 2 years, there was no difference in complication rates or outcome that we could see. Of course, we want to wait for a little bit longer follow-up, [but] it really confirms that in a lot of the early localized breast cancer cases, the hypofractionated short course radiation is probably just as good as the ‘standard conventional’ 5-week radiation.

We have ongoing trials looking into de-escalation of radiation, as well. We have [the phase 3] NRG-BR007 [DEBRA; NCT04852887] and NRG-BR008 [HERO; NCT05705401] trials that are looking into eliminating radiation therapy after lumpectomy in certain [patients with] very favorable risk early-stage breast cancer—so [those] with either low Oncotype [DX Recurrence Score of 18 or less], which is for NRG-BR007, or [those with] HER2-positive [disease] who get appropriate HER2-directed therapy, which is NRG-BR008. We also have [the phase 3] CCTG MA.39: TAILOR RT [NCT03488693], which is looking into [the question of,] for patients with low Oncotype [recurrence score] and with axilla lymph node with limited involvement, can we perhaps de-escalate lymph node radiation? All of this takes a lot of coordination with the surgeons and the medical oncologists. We all need to be on the same page, order the right test like the Oncotype, and the surgery has to be per protocol. Everything has to follow a timeline. So early coordination of care about these [factors] in a multidisciplinary model [is needed]. Starting with the multidisciplinary clinic has been very, very helpful for me to get these patients on the radiation trials.

Stewart: Right, and when you think about these [efforts], [it should be noted that] these are large cooperative studies. [They are] not just a USC-based [studies]; these are institutional based across the United States, and the idea is that you’re going to enroll enough patients that you can assign to either the standard of care [SOC] or the experimental treatment, in order to have enough patients and enough long-term follow-up so that you can really change the SOC to make the SOC even better. I think that these de-escalation interventions are so motivating; they are so sensible. Like you said, there have been a number of trials that have been presented that are really supporting these de-escalation [approaches], which I think is just a very, very smart intervention. And, as you said, when we coordinate with the surgeon and the medical oncologist, it really helps motivate the patients to understand that we don’t know what exactly the right answer is, but we’re going to [provide] the best treatment intervention. The clinical trial participation really makes a lot of sense, and it’s useful for not only the patient, but really the whole world and the whole practice that any patient would be exposed to.

Ye: For sure. I'm sure that goes for system therapy, as well.

Check back tomorrow for the next episode in the series.