At the 2023 ASCO Annual Meeting, Erika Hamilton, MD, Sarah Cannon Research Institute, Nashville, Tennessee, presented on Part A of a phase 2 study evaluating HER3-DXd across metastatic breast cancer subsets, with an aim of determining the patient population most likely to derive the greatest benefit.

HER3-Dxd, or patritumab deruxtecan, has previously shown promising efficacy in HER3-expressing metastatic breast cancer. As Dr Hamilton explains, the overall response rate across all levels of HER3 expression was 35%. She concluded, “HER3 expression does not seem to matter in terms of activity for this drug.” Currently, HER3-Dxd is being evaluated in hormone receptor-positive/HER2-negative, triple negative, and HER2-positive metastatic breast cancer.

Transcript:

Hi, I'm Dr. Erika Hamilton. I lead the Breast Cancer Research program at Sarah Cannon Research Institute at Nashville, Tennessee. This year at ASCO 2023, I'm reporting results from patritumab deruxtecan or HER3-DXd in patients with HER2-negative breast cancer.

HER2-negative really encompasses both patients with traditionally called hormone receptor-positive disease, as well as triple negative breast cancer. This was an investigator-initiated trial study, and so initially we looked at 60 patients regardless of HER3 expression level, either with hormone receptor-positive or triple negative disease. And at this time of analysis we are looking at things in terms of HER3 expression as well as ER expression to decide where we're going into expansions. Another expansion arm besides those is actually in patients that have HER2-positive disease that are post-trastuzumab deruxtecan. So, really asking this question about [antibody drug conjugates] ADC, after ADC and resistance. And this is currently enrolling in study.

What we saw from the 60 patients that were enrolled with HER2-negative disease was really quite remarkable activity. 43% of the patients remained on patritumab deruxtecan for more than 6 months. And again, this is HER3-DXd, so the backbone that you would consider of trastuzumab deruxtecan, but it's targeting HER3 instead of HER2.

We saw that the overall response rate across all levels of HER3 expression was 35%. This actually was a little bit lower for patients that were HER3-high and numerically a little bit higher for those that were HER3-low or HER3-negative, really telling us that HER3 expression does not seem to matter in terms of activity for this drug. These patients were pretty heavily pretreated, a median really of 4 prior regimens, and so having an overall response rate on average of about 35% was really quite impressive.

We also saw that HER3 is highly expressed, with about 65% of patients having high HER3 expression, defined as 75% or greater, with about a quarter of patients having low HER3 expression, 25% to 74%. And patients not having HER3 expression was exceedingly rare, only 4 patients having HER3 expression less than 25%.

Our takeaways really were that HER3 is highly expressed, that it doesn't really matter how much HER3 you have in terms of activity — patients had response rates really quite encouraging across the board — and that this drug really could be appropriate in multiple types of breast cancer. Certainly, in this study, hormone receptor-positive as well as triple negative. But we also have previous data from Iron Crop enrolling HER2-positive patients that showed good activity. And we're currently enrolling HER2-positive breast cancer as Part Z for post-trastuzumab deruxtecan. So, certainly I think this is another antibody drug conjugate that is up and coming, and we're going to be seeing more about this compound.

Source:

Hamilton E, Dosunmu O, Shastry M, et al. A phase 2 study of HER3-DXd in patients (pts) with metastatic breast cancer (MBC). Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 1004.