One of the biggest problems in breast cancer has been the lack of targeted treatments for triple negative breast cancer.
Triple negative breast cancer (TNBC) is defined more by what it’s not than what it is. This type of breast cancer is “negative” for three important receptors: the estrogen receptor, the progesterone receptor and the HER2 receptor. As a result, targeted therapies for breast cancers that do express those receptors do not work for TNBC.
About 10-20% of breast cancers fall into the TNBC category. Those diagnosed with TNBC tend to be younger on average. TNBC also disproportionately affects African American and Hispanic individuals.
This year we’ve seen some encouraging news with approvals of two new treatments–a targeted therapy and an immunotherapy–that work for at least some patients with TNBC.
A Targeted Therapy for TNBC
A targeted therapy is a drug that directly targets cancer cells. In contrast, chemotherapy affects certain types of normal cells in the body too. In theory, targeted therapies should be more effective and have fewer side effects than chemotherapies.
In April 2020, the FDA granted accelerated approval for a targeted therapy called Trodelvy (sacituzumab govitecan) for metastatic TNBC. Trodelvy is an antibody-drug conjugate, meaning that it consists of an antibody (a protein that targets a certain receptor in the cancer cells) linked to a drug that is toxic to the cancer cells.
In the clinical trial of about 100 patients with metastatic TNBC on which the approval was based, one-third of patients receiving the treatment had their tumors shrink by a certain amount. For some, this response was relatively long-lasting.
The treatment can potentially have serious side effects. These include causing abnormally low levels of white blood cells, which increases risk for infection, and severe diarrhea. Patients receiving the treatment need to be monitored closely for signs of these problems.
An Immunotherapy for TNBC
Immunotherapy represents a different approach. Instead of going after cancer cells directly, immunotherapy drugs work by stimulating the patient’s own immune system to fight the cancer.
PD-L1 inhibitors, also called checkpoint inhibitors, work by “releasing the brakes” on the immune system.
As I wrote in a post late last year, in 2019 the FDA approved the first checkpoint inhibitor for use in breast cancer treatment. The drug approved last year is Tecentriq (atezolizumab), and is given in combination with chemotherapy, for patients with metastatic TNBC and tumors expressing the biomarker, PD-L1.
In November 2020, the FDA granted accelerated approval for a second checkpoint inhibitor, Keytruda (pembrolizumab), also to be given in combination with chemotherapy, for patients with metastatic TNBC whose tumors express the marker PD-L1.
Keytruda has already been approved for a number of different types of cancer, but not for breast cancer.
Areas of Concern & Where More Study is Needed
These new treatments are promising and may be helpful for some patients, especially if the expected benefits on which these accelerated approvals were based are confirmed in larger trials.
But a big issue is that a larger proportion of patients in these studies did not receive substantial benefit from them. We need to learn how to make these or other therapies work for more people with TNBC.
Another major concern is that adverse side effects from the treatments can be significant. Trodelvy, the antibody-drug conjugate, can have serious side affects. And with the immunotherapy treatments, the immunotherapy is added to existing standard treatment with chemotherapy rather than replacing it. As a result, patients are subjected to the combined side effects of multiple treatments.
The high cost of new cancer treatments such as these is another problem that urgently needs to be addressed.
And more research is needed to determine whether these or similar new treatments are effective in reducing the risk of recurrence for patients with early stage TNBC. There are studies underway to investigate that.
For More Information
If you would like to read more about these approvals and the related clinical trial findings, here are some informative articles:
- “FDA’s Trodelvy Approval a ‘Big Win’ for Patients with Metastatic Triple Negative Breast Cancer” in Cure Today.
- “Recently Approved and Emerging Therapies for Triple-Negative Breast Cancer” in The Asco Post.
Image Credit: National Cancer Institute via Unsplash