Key Advances in Treating Metastatic Breast Cancer are Helping More Patients

When it comes to the rapidly evolving advancements in treating metastatic, or advanced, breast cancer (MBC), there is one example that has become a game changer. It’s the first U.S. approved I.V. infusion for a newly defined category called “HER2-low” metastatic breast cancer. Just one year ago, the U.S. Food and Drug Administration (FDA) cleared the way for this therapy, trastuzumab deruxtecan (brand name: Enhertu).

It's a treatment that falls under the category of an antibody drug conjugate (ADC), which refers to monoclonal antibodies linked to a chemotherapy drug. Essentially, ADCs act like a homing signal by attaching to the targeted cancer cell (in this case HER2), allowing targeted delivery of chemotherapy. Some ADCs, such as Enhertu have a “bystander effect,” which means the chemotherapy is able to drift across to cells that express lower levels of the target, so-called “HER2-low” breast cancer cells.

This is crucial because roughly half of all metastatic breast cancers are classified as HER2-low, and therefore this is an important new treatment option for a significant number of patients.

 

“Trastuzumab deruxtecan (Enhertu) was initially approved for HER2-positive, and now more recently for HER2-low metastatic breast cancer -- and this therapy has dramatically improved outcomes for our patients in both settings,” explains Reshma Mahtani, D.O., chief of breast oncology at Baptist Health Miami Cancer Institute. “The approval of Enhertu for HER2-low MBC was based on a trial where this therapy was compared to other routinely used chemotherapy drugs and was found to be significantly more effective. While we were already using this highly active ADC for HER2-positive breast cancer, the results of this study led to an expanded indication for the drug in patients with HER2-low MBC.”

This important new treatment option, one year after its approval, has had a remarkable effect.

“We've seen a significant impact,” said Dr. Mahtani. “Given the large numbers of patients with HER2-low MBC, to date many patients have received the drug and are enjoying longer durations of time during which their breast cancer is controlled, while also experiencing an overall good quality of life.”

Enhertu and other ADCs that are under development are proving to be much more effective the previously used chemotherapies because of the precision involved in attacking cancer cells.

“It is not unusual to see patients who have previously received multiple prior types of chemotherapy and have experienced progression of their cancer, who now have significant periods of disease control on Enhertu. It’s really gratifying to see these responses,” explains Dr. Mahtani. “It’s generally well tolerated, is given every three weeks, as an IV treatment. An important point to make is while on treatment there must be vigilant monitoring for a side effect called “interstitial lung disease/pneumonitis,” which can be very serious. Monitoring for symptoms such as cough, shortness of breath and characteristic findings on CT scans is essential while on this treatment. Fortunately, these events are overall quite rare.”

Broadly speaking, the availability of antibody drug conjugates represents a major advance in treatment options for patients with MBC, stresses Dr. Mahtani, who is involved in clinical trials using these therapies.

“Another antibody drug conjugate called sacituzumab govitecan, with the trade name of Trodelvy, is also approved for MBC,” she adds. “This therapy was initially approved for a particularly aggressive form of breast cancer called ‘triple negative breast cancer’ and now more recently was also approved for patients with hormone receptor positive/HER2-negative MBC.

“As new ADCs become available, there are important outstanding questions including whether there will be sequential activity of these treatments, as well as why tumors become resistant or do/do not respond to one drug vs another. These questions are the subject of my research, as I will be leading a multi-institutional clinical trial that will hopefully shed some light on these important questions.”

There are additional novel ADCs under investigation. Dr. Mahtani is part of a large team of physician-investigators at Baptist Health Miami Cancer Institute that is utilizing novel therapies to conduct important cutting-edge clinical research.

“I’m proud to report we just opened our first-line, metastatic triple-negative breast cancer trial with yet another antibody drug conjugate called datopotumab deruxtecan. We're very excited that we have the study open for our patients here in South Florida.”

Triple-negative breast cancer (TNBC) accounts for about 10-15 percent of all breast cancers. The term “triple-negative” refers to the fact the cells don’t have estrogen or progesterone receptors (ER or PR), and also don’t overexpress the HER2 protein on the surface of the cells. TNBC differs from other types of invasive breast cancer because it tends to grow and spread faster, and has traditionally had fewer treatment options, although this is quickly changing as we identify new targets.

For early stage breast cancer patients, there are continued efforts to develop treatments which will decrease the risk of recurrence and progression to metastatic breast cancer.

“For example, many of our early stage TNBC patients require intensive treatments prior to surgery, including chemotherapy and immunotherapy,” explains Dr. Mahtani. “This provides really important information regarding overall prognosis and risk of recurrence. For patients who, despite receiving all that intensive treatment, are still found to have cancer in the surgical specimen, this is somewhat worrisome because we know there is a higher risk of developing metastatic breast cancer.”

Dr. Mahtani is part of two important clinical trials that are addressing the needs of this patient population.

“In one trial patients receive a vaccine which has the promise of reducing the risk of recurrence, and the other trial involves the use of novel targeted treatment based on the genomic make-up of the individual’s cancer,” she explains. “We are hopeful these trials will favorably impact outcomes for these patients who are considered at high risk for recurrence. The good news is death rates from metastatic breast cancer continue to fall as novel treatments become available, and I’m committed to ensuring our patients have access to these cutting-edge therapies.”