Ongoing Research in HER2+ Metastatic Breast Cancer

Transcript:

Megan Kruse, MD: In terms of new treatment approaches for HER2 [human epidermal growth factor receptor 2]–positive metastatic breast cancer at ASCO [American Society of Clinical Oncology Annual Meeting] 2023, 1 of the trials we saw was an update for the PRECIOUS study. This was a phase 3 trial looking at the reintroduction of pertuzumab in treatment of patients with HER2+ metastatic breast cancer in later-line treatment settings after they had received their up-front therapy with taxane-trastuzumab-pertuzumab and an intervening therapy, such as T-DM1 [trastuzumab emtansine] or another chemotherapy-trastuzumab combination. In this updated presentation, we saw that the overall survival level improved when pertuzumab was brought back into later-line treatments compared with other treatment options with trastuzumab and chemotherapy alone. These are significant data to have out there because we don’t usually think about reintroduction of pertuzumab in the later-line setting for patients with HER2+ metastatic breast cancer. It’s a drug that patients will typically see in the adjuvant or neoadjuvant space and then in the first-line metastatic space but not again.

In this same treatment paradigm, we frequently reuse trastuzumab. It’s the backbone of our therapy, and there’s benefit for patients with continuation of trastuzumab beyond progression. These are the first data that suggest there is the same benefit for pertuzumab beyond progression, although it looks like it may be later-line setting in combination with different chemotherapy, not necessarily through every line of treatment, which you might consider with trastuzumab.

The other important thing to point out for this study is that there were some imbalances in the treatment arms, that we’re looking at re-treatment with pertuzumab vs treatment with just trastuzumab and alternative chemotherapy. How we apply these data is a little challenging, but it’s an approach worthy of further investigation. It’s something we should think about when we have patients who have exhausted multiple prior lines of therapy, are still doing well, and have the potential for ongoing quality of life.

Two other posters presented at ASCO 2023 have to do with the treatment of HER2+ metastatic breast cancer, not so much in terms of agent selection but how we deliver and monitor for therapy. The first presentation was from Abstract 2034, which looks at the delivery of HER2-targeted therapy for central nervous system [CNS] involvement with breast cancer, particularly leptomeningeal disease, looking at the route of treatment administration. In this study, the investigators [try to determine] if there was any advantage of giving HER2-targeted therapy from an intrathecal route, an intravenous [IV] route, and an oral route. This is an ongoing topic of debate because we now have oral agents that have significant CNS activity. We also have IV agents that seem to have more significant CNS activity compared with their earlier-generation counterparts.

Is there still a role for the delivery of HER2-targeted therapy via an intrathecal route? Thankfully, this is not a clinical situation that we run into all that often in practice, but when it comes up, it can be hard to know what the best thing is to do. In this poster, the investigators found that there was equal control of the CNS involvement from HER2+ metastatic breast cancer, particularly leptomeningeal disease, when the HER2-targeted agents were given by any route. This devalues the importance of intrathecal administration of HER2-targeted agents for this patient population. That has its own impact on quality of life by having to get lumbar punctures and a particular coordination of care in clinic, whereas the IV and oral drugs are usually part of their standard therapy. If we step back, we recognize that these patients with leptomeningeal disease are often quite ill and don’t have as great of a prognosis as our other patients with metastatic HER2+ breast cancer. Anything we can do to positively impact their quality of life and minimize the burdens of their treatment on their life is a meaningful step.

The second abstract that was presented as a poster that I would like to highlight is the work from [Xiuwen] Guan et al that looks at cardiotoxicity for patients with long-term management with HER2-targeted agents for HER2+ metastatic breast cancer. This is abstract 1034. This study found that patients who were exceptional responders to therapy and on prolonged treatment, which was defined as patients receiving HER2-targeted therapies for 36 months or longer, were going to have a change in their cardiac function measured by left ventricular ejection fraction [LVEF] that often occurred early. The significant drop in LVEF tended to occur within the first 6 months and then recover and stabilize over that prolonged period of treatment, going to 3 years and beyond for some patients.

The standard guidance in this situation is to get an echocardiogram every 3 to 6 months for patients with metastatic HER2+ breast cancer receiving trastuzumab-based therapy. We can counsel our patients to say that the prolonged treatment remains very safe, from a cardiovascular standpoint, and that perhaps we can lighten their load a little by doing echocardiograms less frequently. I’d advocate for at least every 6 months, given this data. We can back off from an every-3-month echocardiogram for some patients, knowing that if we see any change in heart function, it tends to occur early and that patients tend to do well over time.

Transcript edited for clarity.