A cancer treatment set to change how medicine is practiced was approved by the U.S. Food and Drug Administration (FDA) earlier this month, giving women with a newly-defined subtype of breast cancer extended survival rates.
The groundbreaking new drug, Enhertu (trastuzumab deruxtecan), by drugmaker AstraZeneca, was given the all-clear for use in women with unresectable or metastatic HER2-low breast cancer.
“The approval of trastuzumab deruxtecan (Enhertu) for the treatment of metastatic HER2-low breast cancer will have a significant positive impact on a large percentage of patients,” Reshma Mahtani, DO, chief of breast oncology for Baptist Health Wellness and Medical Complex in Plantation, Florida, told Health. “This is the first approved therapy for HER2-low breast cancer and will provide an important new targeted therapy option for many patients.”
Enhertu’s approval is also a step forward in the Biden-Harris Administration’s Cancer Moonshot initiative. Put in place to reduce the rate of cancer deaths and improve the lives of cancer patients and their families, the initiative seeks to better tailor treatments to patients, according to an FDA news release.
“[This] approval highlights the FDA’s commitment to be at the forefront of scientific advances, making targeted cancer treatment options available for more patients,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Evaluation and Research, said in the news release. “Having therapies that are specially tailored to each patient’s cancer subtype is a priority to ensure access to safe and innovative treatments.”
Here's what to know about Enhertu, the specific subtype of breast cancer it's meant to treat, and what the new medication will mean for cancer patients' survival rates.
HER2-Low: A New, Hard to Treat Subtype of Breast Cancer
The type of breast cancer Enhertu is approved to treat is known as HER2-low—a type of breast cancer that “traditionally [has been] quite difficult to treat,” Jane Meisel, MD, a medical oncologist specializing in women’s health at Emory University’s Winship Cancer Institute, told the National Cancer Institute.
Human epidermal growth factor receptor 2—HER2, for short—is a gene that makes a protein found on the surface of breast cells that promotes normal cell growth, according to William Gwin, III, MD, assistant professor of oncology at the University of Washington’s Division of Medical Oncology.
In some breast cancers, however, HER2 can produce too much of those proteins, causing cells to divide and grow too fast. These are known as HER2-positive breast cancers, which account for about 20% of all breast cancers.
Until only recently, the other 80% of breast cancers were labeled as HER2-negative—but it's now thought that 60% of those cancers could better be classified as HER2-low, meaning the cells have some HER2 proteins on the surface, but not enough to be classified as HER2-positive.
"When you think about how much of the breast cancer population this represents, honestly, about 60% of breast cancers [that] are not HER2 positive have some degree of HER2 expression," said Dr. Gwin. "Now that we have this therapy, it can be applied to lots more breast cancers than we originally thought."
A Combination of Two Potent Treatments
Until now, patients with HER2-low breast cancer had more limited treatment options—namely endocrine therapy or chemotherapy—since those intended for HER2-positive patients weren’t effective for the cancer subtype.
HER2-positive patients, for example, already had effective therapies using only monoclonal antibodies, said Dr. Gwin. So this new treatment option is most exciting for patients with low to indiscernible levels of HER2, he added.
"Monoclonal antibodies that bind to the HER2 protein only in this population where it's overexpressed [HER2-positive] were shown to provide benefit in controlling cancer and helping folks live longer," said Dr. Gwin. But in HER2-low patients, those monoclonal antibodies proved ineffective, added Dr. Gwin.
In Enhertu’s case, the medication combines two drugs to work in tandem to target the lower levels of HER2 proteins present, according to Robert Louie, RPh, MBA, executive vice president of clinical services at Remedy One, and pharmacist specializing in managed care.
"Trastuzumab is a monoclonal antibody (a type of biologic drug) targeting HER2 that doesn't work well as a single agent. It's usually combined with other chemotherapy drugs in separate infusions to treat metastatic breast cancer," said Louie, adding that "Deruxtecan is a potent chemotherapy drug."
When combined, Enhertu turns into a sort of "smart bomb," according to Louie. "The trastuzumab portion of the combination attaches to cancer cells expressing HER2 and drops its 'payload' of deruxtecan directly into the cancer cell."
Although Enhertu does at least partially contain a chemotherapy drug, it technically falls into the targeted therapy category, meaning it attacks cancer cells without damaging other healthy cells.
As Brian Wojciechowski, MD, a medical oncologist at Crozier Health in Pennsylvania explained in a recent podcast hosted by BreastCancer.org, Enhertu delivers chemotherapy directly to the cancer cells.
"Not only does it target the chemo more precisely into the breast cancer cell," said Dr. Wojciechowski, "but because it's not going into 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 into the rest of the body."
‘Unheard-of’ Effects on Breast Cancer Survival Rates
When Shanu Modi, MD, the lead researcher on a phase 3 clinical trial of Enhertu’s effects on HER2-low breast cancer, presented her team’s findings during an annual meeting of the American Society of Clinical Oncology, the drug got a standing ovation.
The study, published in the New England Journal of Medicine in July, showed that the drug “resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy.”
For the phase 3 trial, researchers recruited 557 patients with metastatic breast cancer who had the HER2-low subtype. Two-thirds of the patients received Enhertu; the remaining third received their doctor's preferred chemotherapy treatment.
In the patients who received Enhertu, their tumor growth stopped for 10 months—in those who received chemotherapy, tumor growth stopped for five months. Overall, Enhertu patients survived for 23.9 months, compared to the 16.8 months survived by patients on chemotherapy.
A Powerful Drug That’s Not Without Side Effects—or Cost
According to the FDA news release, the most common side effects seen by women in Enhertu’s clinical trials include:
- Decreased appetite
- Musculoskeletal pain
Enhertu was also found to cause interstitial lung disease (ILD) in 12% of the population of the study; three of the 45 people that contracted it had grade 5, or fatal cases of ILD. Patients that choose to undergo Enhertu treatments would be closely monitored for lung inflammation. The drug also carries the risk of embryo-fetal toxicity, and is not recommended for people who are pregnant.
And with any new medication, there is a significant cost associated with the therapy. The per-month cost for a single patient is estimated to be around $13,300, but according to Louie, as a physician-administered drug, it should usually be covered by medical benefits.
With the phenomenal results of the study, FDA approval, and potential for use in so many different types of cancers, Dr. Gwin said he is optimistic about the potential of Enhertu.
"I think it brings…a therapy that looks more effective than probably most, if not all, chemotherapies," said Dr. Gwin, adding that the treatment may "shortly jump our traditional chemotherapy and our sequencing of treatments."
Dr. Gwin added that experts are beginning to think more about "nontraditional targets in hormone receptor and triple-negative breast cancers" to formulate better-designed therapies. "This really can translate," said Dr. Gwin, "into much more beneficial [treatments] for patients dealing with these cancers."