HER3-targeting drug shows promise in metastatic breast cancer | ASCO 2023

In the study, patritumab deruxtecan showed benefit, regardless of HER3 positivity. Dr. Hamilton reported that these findings are consistent with two other clinical trials presented at the 2023 European Society of Medical Oncology Breast Cancer Annual Congress in May.

About patritumab deruxtecan

HER3 is a newer target being looked at in breast cancer. Like HER2, it is a member of the HER receptor tyrosine kinase family (RTK). It works with other RTKs such as HER2 to send signals that promote growth and spread. HER3 expression is more common in metastatic breast cancers than in early-stage disease.

Patritumab deruxtecan (HER3-DXd) is an antibody drug conjugate (ADC) that combines the HER3-targeting drug patritumab and deruxtecan, an anti-cancer drug. The recent FDA approval of two other ADCs to treat breast cancer has energized the breast cancer community about the potential of drugs in this family.

HER3-DXd is approved by the FDA to treat certain metastatic non-small cell lung cancers and is being studied in colorectal cancer. In prior studies in metastatic breast cancer, HER3-DXd decreased tumor size in the cancers of people who had already tried many other breast cancer treatments.

What the study showed

More than one-third (35%) of participants in this clinical trial saw improvement from the use of patritumab deruxtecan, called the overall response rate or ORR. The response lasted for at least six months in nearly half the people whose cancers responded to the drug. The drug showed clinical benefit in 43% of the participants; in this group, those cancers improved or remained stable while on the drug.

The study enrolled 60 adults with HER2-negative locally advanced or metastatic breast cancer, of whom 22% had de novo metastatic breast cancer (diagnosed stage IV from the start). The cancers were hormone receptor-positive or hormone receptor-negative, with 40% of people diagnosed with triple-negative breast cancer.

Nearly two-thirds (64%) of the participants had cancers with HER3 levels greater than 75%, with the remaining mostly HER3-low (25%). Very few people had HER3 levels below 25%. The response rates varied by HER3 activity, suggesting the cancer does not have to be HER3-positive to benefit from this drug.

In general, people tolerated the drug well with no key safety concerns. About 15% of participants had a dose reduction, and just one person lowered the dose more than once. The most common side effects were nausea, fatigue, and diarrhea. Nausea occurred most often but in only half of participants. Two people developed serious but not fatal side effects, both related to the lungs.

What does this mean for you?

This report offers hope that a HER3-targeting ADC treatment holds promise for treating metastatic breast cancer. In her closing remarks, Dr. Hamilton said the data support the potential to introduce patritumab deruxtecan into the clinic for people with all types of metastatic breast cancer. It’s possible that could happen before the drug moves into testing through a phase III clinical trial.

These results, alongside findings from two other clinical trials, suggest that people with varying HER3 levels might benefit from this drug. In this trial, people with both HR- and HR+ cancers saw improvement, although the response rate was higher among people with HR+ metastatic breast cancer compared to triple-negative breast cancer.

Our report summarizes findings from the first part of a three-part study. The clinical trial is ongoing and continues to enroll participants for the next two parts of the trial. Look for more updates to come, including results related to the benefits or drawbacks of treating a cancer that did not respond to one ADC with another ADC. This information could be very relevant in metastatic breast cancer, where people typically cycle through treatments, moving on if they stop working.

Talk with your doctor if you are interested in learning more about HER3-DXd or joining the clinical trial.