Unmet Needs and Clinical Pearls in the Treatment of HER2+ mBC

Transcript:

Megan Kruse, MD: The last couple of years have been a tremendously exciting time for the management of patients with HER2 [human epidermal growth factor receptor 2]–metastatic breast cancer because we have many new treatment options that are very successful and have made a huge difference in the quality and length of our patients’ lives. There are still some unmet needs in this patient population that are important to focus on. Our newer therapies, while active in the brain metastasis setting, still have a lack of data for patients with leptomeningeal disease. I’d love to see more data for those patients to verify that we’re doing the right thing and have them included in clinical trials.

It’s also tough to know what to do for patients who have comorbidities, knowing that some of our newer therapies have toxicities that we haven’t had to consider before. The main 1 to highlight is the risk of pneumonitis and ILD [interstitial lung disease] with trastuzumab deruxtecan. This drug isn’t recommended for use in patients with any preexisting pneumonitis or ILD issues. It’s hard to know how to treat our patients with significant preexisting pulmonary comorbidities in this situation because the medication is so active, and we want to give patients the benefit of all the therapy. This highlights an unmet need in knowing how to treat patients in a real-world setting, which is a bit different from the criteria we have for inclusion on clinical trials. It also highlights the importance of having attention given to systematic development of toxicity monitoring and management in our clinical practices. This is something a lot of minds are thinking about in the world as we use more trastuzumab deruxtecan but also other agents that have a risk of pneumonitis-like immunotherapy and the CDK4/6 inhibitors.

In the management of HER2+ metastatic breast cancer, there are a few key things to keep in mind. The first is that these patients are at significant risk of developing brain metastases. Knowing which patients have brain metastases, following for them, and knowing which therapies are active for brain metastases is crucial. I encourage all in our community to think about incorporation of CNS [central nervous system] imaging for these patients. If you find brain metastases, work in a multidisciplinary fashion with our colleagues from radiation oncology to determine which patients are best suited for local therapy and which might be able to go straight to a medical therapy such as the tucatinib-based regimen, knowing that this is active for patients with untreated active brain metastases.

It’s important for these patients that we monitor key toxicities over time and empower them to report symptoms of concern to us. There’s the risk of pneumonitis and ILD with trastuzumab deruxtecan. This can present very subtly, with a prolonged dry cough, some dyspnea, increasing fatigue, or decreased exercise capacity. These are things we might attribute to several other complications that arise from metastatic breast cancer or metastatic breast cancer treatment. I’d like providers to make sure we keep our index of suspicion at the forefront of our minds and empower our patients to know what the symptoms of concern are so they can report them early and we can intervene early, because it makes a big difference for safely managing these agents.

Lastly, I’d like to make sure that all our providers know that there are many ongoing trials in this space, looking at different combinations of agents and continuing to follow our patients in the long term. This is important because, as you’ve heard in our discussion, the key issues of sequencing and how we best utilize the new agents at our disposal are going to be the biggest questions as the field moves forward.

Transcript edited for clarity.