- The Food and Drug Administration (FDA) approved AstraZeneca’s Enhertu to treat HER2-low breast cancer.
- Enhertu is the first targeted treatment for this subtype of breast cancer.
- Following the Enhertu trials, the treatment nearly doubled the median progression-free survival period compared to the patients who received a different treatment.
In February 2022, the Biden Administration announced that it wanted to reduce cancer death rates by 50% over the next 25 years through the Moonshot Cancer program. Part of that program includes “streamlined cancer-related decision-making” at the Food and Drug Administration (FDA).
As a result of the program, a new treatment for breast cancer received FDA approval. The treatment, Enhertu (fam-trastuzumab-deruxtecan-nxki), directly targets the HER2-low breast cancer subtype.
HER2-low breast cancer
HER2 is a protein that contributes to how breast cells grow, and when HER2 does not work correctly, it can cause breast cancer tumors to grow more rapidly. In the past, doctors classified breast cancer tumors as HER2-positive or HER2-negative based on immunohistochemical (IHC) scores given during cancer screening.
However, recent research shows that there is a subtype called HER2-low, as some people who tested HER2-negative can still have low levels of HER2 and cancers that have metastasized or can’t be removed. These patients were previously precluded from receiving certain treatments available to HER2-positive patients, and would have received endocrine therapy or traditional chemotherapy before the Enhertu FDA approval.
According to the FDA release, doctors will diagnose around 287,850 new cases of female breast cancer in 2022. Since around 80% of those would previously have tested HER2-negative, and 60% of those cases would now test as HER2-low, treatments could potentially expand for more than 100,000 breast cancer cases.
How Enhertu works
According to the FDA, Enhertu is an intravenous infusion that is indicated for HER2-low patients with “unresectable (unable to be removed) or metastatic (spread to other parts of the body) HER2-low breast cancer.”
Enhertu falls under the targeted therapy category, so it attacks cancerous cells without damaging healthy cells. The medication specifically attacks cells with the HER2 protein.
Dr. Brian Wojciechowski, an oncologist at Crozer Health in Pennsylvania, talked about how Enhertu works during a podcast hosted by BreastCancer.org.
“The antibody-drug conjugate part … is attached to a chemo drug called deruxtecan, and it kind of acts like a Trojan horse,” commented Dr. Wojciechowski.
Dr. Wojciechowski mentioned that this treatment is beneficial because it delivers the chemotherapy component of Enhertu directly to the cancer cell.
“Not only does it target the chemo more precisely into the breast cancer cell, but because it’s not going to the rest of the body, it allows us to give a chemo drug that’s much more powerful than other chemo drugs that would go to the rest of the body,” he said.
Per the prescribing information for Enhertu, patients who receive the treatment receive an infusion every 21 days. During the trial, patients received Enhertu for a median of 8 months.
Effectiveness of Enhertu
During the drug’s Phase 3 DESTINY-Breast04 trial, researchers compared patients who were prescribed Enhertu to those who were prescribed their physician’s choice of chemotherapy medication.
The trial studied 557 adult patients with HER2-low breast cancer. Of the patients, the researchers randomly selected 373 to receive Enhertu and 184 to receive their doctor’s treatment choice.
The patients who received Enhertu had a median progression-free survival of 9.9 months. The patients who were given their doctor’s treatment choice had a median progression-free survival of 5.1 months.
In comparison, patients treated with Enhertu saw their cancer managed for almost twice as long.
Additionally, the overall survival rate for the patients who received Enhertu was 23.4 months whereas the overall survival rate for patients who received their physician’s treatment of choice was 16.8 months.
Enhertu side effects
Enhertu can cause a number of side effects and reactions. Some of these side effects can be life threatening, which necessitated a boxed warning for Enhertu.
The most common side effects include:
- nausea
- decreased white blood cell count
- fatigue
- vomiting
- musculoskeletal pain
Approximately 28% of patients who received Enhertu during the trial had severe adverse reactions, and 16% of the trial patients had to stop receiving Enhertu treatments permanently.
The most common severe reactions were interstitial lung disease (ILD), pneumonitis, and sepsis. Several people died during the trial because of severe adverse reactions, including three people who died due to ILD/pneumonitis.
Expert opinions
Dr. Parvin Peddi, a medical oncologist at Providence Saint John’s Health Center in Santa Monica, CA, spoke with Medical News Today about Enhertu’s approval.
“A new group of patients with HER2-low breast cancer can qualify for this treatment after a trial of chemotherapy,” said Dr. Peddi.
Dr. Peddi is also director of Breast Medical Oncology for the Margie Petersen Breast Center at Providence Saint John’s Health Center.
“Anti-HER2 medications are now so good that they can help in patients traditionally considered HER2-negative but who have some HER2 positivity,” said Dr. Peddi. “It’s not without side effects and requires careful monitoring, but it can now benefit a much larger patient population than just the HER2-positive breast cancers.”
– Dr. Parvin Peddi
During the BreastCancer.org podcast, Dr. Wojciechowski mentioned how important the trial for Enhertu was. He mentioned that typically drugs are compared to placebos during trials and that Enhertu was compared to existing approved treatments.
“It’s less common to actually see an overall survival benefit, and when you do see overall survival — and overall survival is how long people actually live with the cancer,” remarked Dr. Wojciechowski. “When you see an overall survival difference, that’s considered pretty remarkable, and in this case, the overall survival difference was 23.4 versus 16 months for the whole group.”
Dr. Bhavana Pathak, a medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, CA, also spoke with MNT about Enhertu.
“This approval is practice changing and received a rare standing ovation at our oncology society’s annual conference for the work by Dr. Shanu Modi,” said Dr. Pathak. We now have a new drug to treat a large population of women who were otherwise previously thought to be negative for the HER2 protein on their breast cancer,” Dr. Pathak noted.
Dr. Pathak, who is also a board certified internist and hematologist at MemorialCare Cancer Institute, called Enhertu “quite efficacious.”
“I think we should rethink how we test and report HER2 results. It is beautiful to see this type of progress with efforts by the Cancer Moonshot project,” she added.
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