Improving Outcomes in Patients With HER2+ Metastatic Breast Cancer: Applying Evidence to Clinical Practice - Episode 12
Expert panelists discuss insights on HER2+ BC from the 2022 ASCO Annual Meeting including safety updates from DESTINY-BREAST03, data on the potential prognostic value of TILs, and trials on local therapy for oligometastatic disease.
Erika Hamilton, MD: Tiffany, what data from this year’s  ASCO [American Society of Clinical Oncology] [Annual Meeting] may have been most compelling in HER2 [human epidermal growth factor receptor 2]-positive [disease]? [What have] you seen that’s piqued your interest?
Tiffany Traina, MD: There are a couple of things. One is just some reassuring data about the lower rates of interstitial lung disease with trastuzumab deruxtecan, so updates in DESTINY-Breast03 [NCT03529110] but also seeing an expanded role for trastuzumab deruxtecan outside of HER2-positive [disease] and in the HER2-low space. [It’s] hard not to acknowledge that from the plenary. We saw some interesting data about the prognostic value of [tumor-infiltrating lymphocytes] in HER2-positive disease. It’s not something that’s practice-changing tomorrow, but it’s interesting information.
Erika Hamilton, MD: As I was reflecting on DESTINY-Breast04 [NCT03734029], which is a little off topic, but I feel like [for] the past 2 decades, we’ve [been] subsetting, profiling, and figuring out who gets what, and then a drug comes along. Now I’m thinking, “Well, should we just give it to everybody? Do we really need to be testing for the [immunohistochemistry]?” It’s kind of full circle.
Rita Nanda, MD: It’s exciting to have that option for patients with hormone receptor-positive [and] triple-negative disease.
Erika Hamilton, MD: Maybe exciting is not the right word, but do you want to tell us a bit more about radiation for oligometastatic disease? Do you think that impacts what we do? Do you think that says we’re continuing to do what we are [doing] and only for select patients?
Ryan Jones, MD: [It’s] a concept that’s now over 30 years old at this point. Patients present with limited sites of metastatic disease, and [we] are recognizing that they [generally] behave differently compared [with] patients presenting with a higher number of metastatic sites at diagnosis. I am a believer [in] the concept of that limited burden of metastatic disease, and might local therapy help [with] the concept of a genetic variability of these tumors? Might we help more stubborn oligoprogressive sites? I trained under some of the leading pioneers in that oligometastatic disease space for lung cancer specifically. We now have trials that have mixed together histologies [that] are showing positive results. [We] have some older surgery literature for breast cancer, suggesting a [possible] benefit for metastasectomy of patients [with] oligometastatic breast cancer. As I mentioned, NRG-BR002 [NCT02364557] from [the] ASCO [meeting] this year gives us pause that it’s not clear yet [whether] any breast cancer subgroup would benefit from aggressive local therapy in the de novo setting. As the drugs improve, I’m curious [whether] we can play a role with more stubborn sites in these patients [in whom] we’re trying to extend survival [for] as long as possible. You all have just been [doing] so well in drug development, where our role is fading.
Erika Hamilton, MD: Does it change your practice at all? Would you still consider it for the select patient?
Tiffany Traina, MD: There’s so much nuance to interpreting these different trials, and in looking at them [and] trying to understand [whether] this particular study [was] open to oligoprogression. The NRG-BR002 [trial] required stable disease for a prolonged period of time. Those are the folks I’m less inclined to call on radiation to solve a problem, because I think the systemic therapy may be keeping things under control. Certainly, if there’s any possible palliative benefit or possibility there, I’m inclined to call in the radiation oncologist, because it can be incredibly tempting to chase after the 1 or 2 spots that might be remaining on a scan. But I also wonder [whether] there’s something to the biology of that oligometastatic disease that systemic therapy will keep quiet. I don’t have an answer—a good one, at least.
Erika Hamilton, MD: That’s fine. I’m a little biased because I presented it, but [from] the safety update of DESTINY-Breast03, I think we all knew trastuzumab deruxtecan may [have] had some extra [adverse] effects, but looking at the exposure-adjusted incidence rates or the risk per patient year put those into context of the benefit. The exposure-adjusted incidence rates of grade 3 adverse events or serious adverse events were lower. That was a little reassuring to me, and I was even a bit surprised that the time to hold or time to dose reduction was so much longer for [trastuzumab deruxtecan] than [trastuzumab emtansine]. I think we certainly have to stay on top of [adverse] effects such as nausea and vomiting. I also thought [it] was interesting that it was pretty stable over time. It wasn’t like it goes away, assuming you really need to keep those supportive care medicines on board.
Transcript has been edited for clarity.