Updates from ASCO 2023 in HER2+ Metastatic Breast Cancer

Transcript:

Megan Kruse, MD: This next abstract from ASCO [American Society of Clinical Oncology Annual Meeting] 2023 from [Jean-Sebastien] Frenel et al looks at a real-world utilization of tucatinib-based regimen following trastuzumab deruxtecan in a multicenter French population. These are important data for us, as treating physicians, because sequencing remains a large question when it comes to the second- and third-line treatment of patients with metastatic HER2 [human epidermal growth factor receptor 2]–positive breast cancer. In this study, there was maintained efficacy of the tucatinib-based regimen after use of trastuzumab deruxtecan. It was a relatively small study of 101 patients, but the results for the efficacy of the tucatinib-based regimen are what you’d expect in a patient population that’s being treated in the third-line setting or beyond. If patients are going to receive both treatments in their treatment course, we can be reassured that if we give trastuzumab deruxtecan first followed by the tucatinib-based regimen, then we’re not losing out on efficacy of the regimen.

This next abstract is a look at the real-world characteristics and treatment patterns for patients who have received tucatinib for HER2+ metastatic breast cancer. This is work done by Dr [Carey] Anders et al, presented at ASCO 2023. In this study, about 75% of the patients were treated in the real-world setting, mostly in the third and fourth lines for their HER2+ metastatic breast cancer but also in the second or an even later line. About 75% of these patients had brain metastases. This signals that this is potentially a higher-risk population than we saw in the original HER2CLIMB study. It also goes to show that clinicians are feeling confident about using this regimen in patients with brain metastases and perhaps favoring this regimen over other regimens for patients with brain metastases.

The next 2 abstracts I’d like to highlight are trials in progress. The first is the HER2CLIMB-05 study by Dr [Erika] Hamilton et al. This study looks at the use of tucatinib as an additional therapy for patients receiving trastuzumab and pertuzumab maintenance in the metastatic breast cancer setting. This takes patients who have received 4 to 8 cycles of their initial therapy in the first line for metastatic HER2+ breast cancer. They are typically patients who are receiving a taxane along with trastuzumab and pertuzumab. After 4 to 8 cycles, many of us would drop the chemotherapy component and continue with trastuzumab-pertuzumab maintenance until there was progression of disease. In that maintenance phase, the randomization in this trial comes in, where patients are randomized to receive tucatinib in combination with the maintenance trastuzumab-pertuzumab or a placebo in combination with those maintenance therapies. The key end point is progression-free survival. The other important thing about this trial in progress is that patients must have CNS [central nervous system] or brain imaging as they’re entering and continuing on a trial. This is a high-risk population for brain metastases, and we’re particularly interested in the activity of tucatinib in preventing brain metastases for these patients with metastatic breast cancer. There are going to be some predefined end points looking at the CNS activity of this agent and the CNS control we see with this treatment regimen.

The second trial in progress that I’d like to highlight is the UCLA B-13 trial, which is an effort from Dr [Nicholas Patrick] McAndrew and colleagues at UCLA [the University of California, Los Angeles]. It looks at the use of ribociclib, tucatinib, and trastuzumab and the treatment of patients with metastatic HER2+ breast cancer. This is a phase 1 study looking at dose finding for this combination and dose escalation of ribociclib in this situation. It will go on to form the foundation for a phase 2 trial in patients with early stage HER2+ breast cancer in the neoadjuvant setting. This is a very interesting trial and a potentially interesting combination for us as clinicians because we’re very familiar with the use of CDK4/6 inhibitors and ribociclib in the treatment of hormone receptor–positive HER2-negative metastatic breast cancer. But the CDK4/6 inhibitors have not made their way into regular use from regular treatment for HER2+ metastatic breast cancer. In the preclinical setting, when these drugs were first investigated, there was a large signal of efficacy, not only for the hormone receptor–positive patients but also for the HER2+ patients. It will be nice to see some data in this space with CDK4/6 inhibitors. It’s certainly a novel combination of the CDK4/6 inhibitors with a tyrosine kinase inhibitor as well as trastuzumab.

Transcript edited for clarity.