To discuss treatment options beyond the frontline setting, Erika Hamilton, MD, presents the clinical scenario of a 43-year-old woman with HER2+ mBC who progressed on paclitaxel/trastuzumab/pertuzumab.
Erika Hamilton, MD: I'm going to talk a little bit about this next case, which was a case from my clinic. This is a 43-year-old woman who presented with de novo metastatic disease, determined to be beat bone pain, and ultimately that revealed quite extensive bone metastases. Markers: she was ER (estrogen receptor)-negative, PR (progesterone receptor)-negative, and HER2 amplified by FISH (fluorescence in situ hybridization). Initially, she received paclitaxel, trastuzumab, and pertuzumab with a great response. This was back in 2018, and ultimately did well on that for a couple of years.
In 2020, she had progression in the spine and received radiation to the paraspinal soft tissue: a mass that was causing a lot of that pain for her. In 2020, she initiated second-line therapy with T-DM1 (trastuzumab emtansine), and ultimately, she developed brain metastases. She had stereotactic radiosurgery (SRS) to 3 lesions in the brain. The largest was 1.3 centimeters. Then in August 2020, she started on capecitabine with trastuzumab and tucatinib. She did well on that for quite some time. Then in 2021, she had progression in the liver, but luckily her brain remained stable at that time. She started trastuzumab deruxtecan in March of 2021. She actually tolerated it pretty well. She did have some grade 1 nausea, but once we found the right antiemetic regimen for her, she did quite well and had some grade 1 fatigue. She had shrinkage of her liver lesions, which were actually pretty substantial, which was exciting. [There was] some improvement on her bone scans as well, and [the] brain has continued to be stable over time and she's still on trastuzumab deruxtecan. Maybe Rita and Tiffany, would you comment on how you might have treated this patient? Is this somebody that is representative of somebody you see in clinic?
Rita Nanda, MD: Yeah. I have definitely seen patients like this. I think, as we all are having a sense, the vast majority of our patients are de novo metastatic now, so [this is] pretty consistent with what I've seen. I think we know from the HER2CLIMB trial (NCT02614794) that patients with brain metastases have actually had regression of their brain metastases on tucatinib-based therapy. I actually had 2 patients who participated in that trial who went in with small brain metastases that regressed on therapy. I subsequently found out after the fact. When they were unblinded, they were tucatinib. I think now, if I saw a patient like this, I might actually not do SRS and actually just treat with the HER2CLIMB [trial] regimen, see how it goes, and radiate if needed.
Erika Hamilton, MD: That's a good point for somebody like this. Hindsight's always 20/20, but she had great control and [did] well for a long time. The long-term effects of radiation can sometimes be really challenging, particularly for our younger patients [who] really want to be higher functioning. She's got several small kids at home. What about you, Tiffany? Would you have done anything differently? How would you be thinking about this?
Tiffany Traina, MD: As I was listening to this, one of the areas that is a question mark for me is this: when you said she progressed in the CNS (central nervous system) with these small lesions, what was happening extracranially? Today, guidelines would suggest that, if everything else was quiet, we could just do a local therapy and then maintain that systemic treatment. Now, knowing the benefits of tucatinib, I think we all wonder is this just an opportunity to change up the systemic therapy hoping that we'll get better CNS control? I think this is tricky. Something that really gets personalized. If the regimen is otherwise managed so well and our patients are feeling well, [if] our radiation colleagues can address those small spots, maybe we’re able to stretch that systemic therapy longer before we need to make a change.
Erika Hamilton, MD: Absolutely. I think that, when you're thinking about treatment for HER2+ disease, a lot goes into that. How long have they benefited on their last therapy? Do they or do they not have brain metastases? What [adverse] event profile are you looking for? Disease burden sometimes can impact my decision about whether I'm using trastuzumab deruxtecan or something different as well like tucatinib or capecitabine and how I'm going to order that. Rita, what about trastuzumab deruxtecan in HER2+ breast cancer, specifically around brain metastases? What evidence do we have there?
Rita Nanda, MD: Well, I think it's really exciting when we think about how the vast majority of patients with metastatic HER2+ breast cancer will actually develop CNS disease over their disease journey, it's nice to know that we've got multiple options now that can result in response to systemic therapies. We have some data now with trastuzumab deruxtecan from the TUXEDO trial (NCT04752059) [and] from the subgroup analysis of the DESTINY-Breast01 trial (NCT03248492) that demonstrate that these agents have pretty substantial intracranial responses in the 50% to 70% range, even for individuals who have previously received radiation therapy. I think it's exciting to see that it's not just radiation that we have to go to anymore, but that we've got systemic therapies that adequately penetrate the CNS to help control disease.
Erika Hamilton, MD: I think you bring up a really important point there because, conceivably, we wouldn't have really thought that these large antibody-drug conjugates would've crossed into the brain wall. We're clearly seeing that brain metastases themselves, [with] the prior radiation, allow drugs like trastuzumab deruxtecan to have great activity [with] upwards of 70% response.
Transcript has been edited for clarity.