A new treatment option for the most common subtype of breast cancer is generating excitement among oncologists because it appears to be more effective — and cause fewer side effects — than traditional chemotherapy.
The medication is sacituzumab govitecan (Trodelvy), which the U.S. Food and Drug Administration (FDA) recently approved for advanced forms of a type of breast cancer commonly referred to as HR-positive/HER2-negative — an abbreviation for advanced hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative.
The drug was previously approved for triple negative breast cancer, a subtype that doesn’t respond to treatment with hormone therapy or certain targeted cancer drugs.
HR-positive/HER2-negative tumors are the most common subtype of breast cancer, according to the National Cancer Institute (NCI). Nearly all patients survive at least five years when this type of breast cancer is caught very early, and more than 90 percent of them live this long when tumors have only spread to some surrounding tissue near the breast, according to the NCI.
But five-year survival odds drop to about 32 percent for patients with tumors that have metastasized, or spread to more distant tissue and organs, according to the NCI.
In a pivotal clinical trial, Trodelvy helped patients with advanced cancer live an average of 3.2 months longer than conventional chemotherapy, its developer Gilead Sciences said in a statement. In addition, 21 percent of those on Trodelvy had little evidence of cancer progressing after one year, compared with just 7 percent of patients on conventional chemotherapy.
Here, Jason Mouabbi, MD, an assistant professor of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston, answers the most pressing questions about Trodelvy.
Q: How does Trodelvy work to treat breast cancer?
A: Trodelvy is part of this new generation of medication called antibody drug conjugates. It’s a better way of delivering chemotherapy to cancer cells. With conventional chemotherapy, you get an IV line and deliver treatment that kills everything indiscriminately — both healthy cells and the cancer cells. Sometimes the treatment can lead to a lot of side effects because it is killing a lot of healthy cells.
Trodelvy is basically an antibody that has a chemotherapy bound to it. The antibody binds to a specific protein, Trop2, that is more expressed [produced] on cancer cells than on healthy cells. When the antibody in Trodelvy binds to Trop2, it gets into the cancer cell and then releases its chemotherapy payload, leading to the death of the cancer cell.
This is as close as we get in cancer to a silver bullet. With chemotherapy, we can’t distinguish between cancer and healthy cells. Now with Trodelvy we can deliver chemotherapy directly to cancer cells and minimize killing the healthy cells.
Q: Who can take Trodelvy for breast cancer?
A: It was first approved for triple-negative breast cancer in 2020. The new, expanded approval for Trodelvy covers people with advanced hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR-positive/HER2-negative) breast cancer. HR-positive/HER2-negative breast cancer is more common.
Right now, Trodelvy is for people with advanced breast cancer. Clinical trials are under way for early-stage breast cancer.
Q: Before Trodelvy was approved for HR-positive/HER2-negative breast cancer, what were the best treatment options?
A: Patients with HR-positive breast cancer start their treatment journey with endocrine, or hormone, therapy. By doing this, we often can achieve durable [lasting] responses. However, sometimes for some patients the cancer becomes resistant to hormone therapy. Once these patients stopped responding to hormone therapy, then we’ve only been able to give them conventional chemotherapy. This means their body gets exposed to chemotherapy that doesn’t discriminate between healthy cells and cancer cells, and it can make them quite sick.
Q: How does Trodelvy compare with conventional chemo?
A: The true value of Trodelvy is it allows us to target cancer cells more specifically and spare healthy cells. This means far fewer side effects than chemotherapy. Trodelvy is also much more effective than conventional chemotherapy. Because of the way it targets only cancer cells, you can potentially deliver a much higher dose of chemotherapy to individual cancer cells with Trodelvy than with traditional chemotherapy. Infusions for treatment are also much shorter and less frequent with Trodelvy.
Q: Is this game-changing?
A: It is definitely game-changing. The class of medicines that Trodelvy belongs to, antibody drug conjugates, has really revolutionized the field. It changes everything. It opens a new era not only for breast cancer but for other cancers. I have no doubt we are going to get different antibody drug conjugates that target different proteins or target different aspects of the cell division machinery. We are just at the beginning of this. I expect Trodelvy to be the first of many drugs like this.
Q: How concerned should patients be about the FDA black box warning that Trodelvy can pose serious risks of diarrhea and dangerously low white blood cell levels?
A: I want to reassure patients. Yes, it’s a black box warning, and that can sound scary. But side effects from Trodelvy are generally not as bad as conventional chemotherapy and most oncologists can manage the side effects.
I don’t see diarrhea that much with Trodelvy, honestly, and when it happens, it can be managed easily with over-the-counter medication like Imodium (loperamide).
As far as white blood cells, not every patient will have a problem with this. We test every patient before they start Trodelvy. If they do experience a problem with low white blood cell counts, then we can add a treatment to stimulate the bone marrow to produce more white blood cells. I want to stress that Trodelvy is much better tolerated by patients than traditional chemotherapy.
Q: What’s the best way for patients to ask their doctor about Trodelvy, especially if they’re worried about seeming pushy or rocking the boat?
A: Any time a patient qualifies for conventional chemotherapy, they should ask if they can substitute this for an antibody drug conjugate. It’s a fair and reasonable thing to ask. As a patient you can ask simply, “Is this right for me?” or “Is this an option for me right now?” and it may turn out that even if you’re not currently a candidate for this treatment, it’s possible you might be in the future.
Q: What’s the bottom line on Trodelvy?
A: Compared to chemotherapy, Trodelvy is much better tolerated and much more effective. Patients stick with treatment more often with Trodelvy than they do with chemo, too, because so many times side effects from chemotherapy make them want to stop. People also have a much better quality of life during treatment with Trodelvy — they’re often able to continue their hobbies and their lives.
