In a recent clinical trial, Enhertu performed better than a similar drug that is the current standard treatment for patients with some types of advanced metastatic breast cancer.
The Clinical Trial
In the trial, the researchers wanted to see how Enhertu performed compared to a similar drug called Kadcyla (ado-trastuzumab emtansine), which is the standard treatment for patients with advanced metastatic breast cancer for whom other treatments have failed.
The trial included 524 patients with HER2-positive metastatic breast cancer. All of the patients had previously been treated with trastuzumab (a chemotherapy drug) and taxane (a drug that stops cells from dividing).
The findings showed that Enhertu reduced the risk of disease progression or death by 71.6%. An independent analysis of the trial’s data found that the median time to when a patient’s cancer had progressed or to when the patient died was 25.1 months for Enhertu compared to 7.2 months for Kadcyla—a risk reduction of 73.5%.
These findings add to data from the first clinical trial that showed Enhertu benefited patients who had previously been treated with Kadcyla.
AstraZeneca announced the trial’s results on September 18, and the findings were also presented at the European Society for Medical Oncology meeting.
Kadcyla uses another version of the same monoclonal antibody that’s in Enhertu, but it’s linked to a different chemotherapy agent. Kadcyla is the current standard of care for patients with advanced metastatic breast cancer when other treatments have failed.
The Need for New Therapies
Shanu Modi, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City who was not involved in this study, tells Verywell that the findings are important because the study was “the first randomized trial” of Enhertu and that the drug showed “significant efficacy advantage over the current second-line standard of care therapy.”
Modi says that a difference in a drug’s benefit of this magnitude is not frequently seen, which makes the data “extremely compelling.”
Dorraya El-Ashry, PhD, the chief scientific officer at the Breast Cancer Research Foundation, was also not involved in the trial, but tells Verywell that “people with metastatic disease, no matter the subtype, are in critical need of new therapies.”
El-Ashry says that overall, the results of the trial are “very promising and provide patients with an added tool to treat a life-threatening disease.”
How Does Enhertu Work?
Enhertu is in a class of drugs called antibody-drug conjugates. These drugs work by having the antibody target the cancer cells, then delivers the chemotherapy drug directly to them (like a plane carrying a payload of bombs to a target). With this type of treatment, chemotherapy can be more precisely aimed at cancer cells.
“The difference between these two antibody-drug conjugates really lies in the advancements made in the linker-payload technology,” says Modi. A linker-payload is the chemical bond between the antibody and drug.
A less common but serious risk of Enhertu is an inflammatory lung condition called interstitial lung disease which causes difficulty breathing and can lead to heart problems.
With Enhertu, Modi says that the payload is a different chemotherapy drug—one that is not commonly used to treat breast cancer.
“It has twice as many molecules of chemo linked to each antibody,” says Modi. “So it delivers much more chemo to the cancer cells.” From there, it produces a “bystander effect,” meaning that it can pass through the membrane of HER2 positive cells and kill neighboring cancer cells that might be HER2 negative.
Does Enhertu Improve Survival?
Based on previous data, the researchers already knew that Enhertu can extend the progression-free survival (the length of time before a patient progresses or has a recurrence) for patients with cancer that cannot be surgically removed and for whom other anticancer treatments have failed or stopped working.
El-Ashry says that the results of the recent trial are still only preliminary findings; they only show that the time to progression has increased and do not show if there is an increase in the overall survival of the patients.
“These are interim results and so the overall survival (OS) rate—while trending towards being increased—did not reach significance,” says El-Ashry.
Approving Enhertu for Earlier Use
Currently, Enhertu is only approved as a third-line treatment (which means that it’s not used until other drugs have been tried and have failed) for some patients with HER2-positive breast cancer.Modi says that not every type of breast cancer is HER2 positive—about 15% to 20% are. According to El-Ashry, there are currently “168,000 women and men living with metastatic breast cancer.”
The monoclonal antibody component of Enhertu, trastuzumab, has been approved for treating breast and gastrointestinal cancers for years. One brand name of the drug is Herceptin.
Before Herceptin, HER2-positive breast cancers had an increased risk of metastasizing and patients had a poor overall chance of survival. El-Ashry says that targeted HER2 therapies have significantly changed the outcomes for these patients.
The results of the recent clinical trial may help Enhertu get approved for use earlier in treatment as second-line therapy for HER2-positive breast cancer.
“The is significant in that it adds Enhertu to the armamentarium of new, more effective HER2 directed therapies for metastatic HER2 positive breast cancer,” says El-Ashry. “The next step will be to study the drug’s overall survival benefit to gauge its effectiveness.”
