Treatment with the immunotherapy medicine Keytruda (chemical name: pembrolizumab) plus chemotherapy before surgery, followed by Keytruda alone after surgery improved event-free survival better than chemotherapy alone in women diagnosed with early-stage triple-negative breast cancer, according to the latest results from the KEYNOTE-522 study.
The results were presented on July 15, 2021, at the European Society for Medical Oncology (ESMO) Virtual Plenary 2021 and published online at the same time in the journal Annals of Oncology. Read the abstract of “KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab + chemotherapy vs. placebo + chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC.” (PDF)
Doctors call treatments given before surgery neoadjuvant treatments and treatments given after surgery adjuvant treatments.
For this study, event-free survival means the length of time a person lived without:
- the cancer growing
- the cancer coming back in a part of the body away from the breast (distant recurrence)
- receiving a second primary cancer diagnosis
About triple-negative breast cancer
Triple-negative breast cancer is:
Triple-negative breast cancers are usually more aggressive, harder to treat, and more likely to come back (recur) than cancers that are hormone-receptor-positive or HER2-positive. Triple-negative breast cancers don’t usually respond to hormonal therapy medicines or medicines that target the HER2 protein.
Keytruda is a type of immunotherapy medicine known as an immune checkpoint inhibitor. To start an immune response to a foreign invader, the immune system has to be able to tell the difference between cells or substances that are “self” (part of you) and “non-self” (not part of you and possibly harmful). Your body’s cells have proteins on their surfaces or inside them that help the immune system recognize them as “self.”
Some of the proteins that help your immune system recognize “self” cells are called immune checkpoints. Cancer cells sometimes find ways to use these immune checkpoint proteins as shields to avoid being identified and attacked by the immune system.
Immune system cells called T cells roam throughout the body looking for signs of disease or infection. When T cells meet another cell, they analyze certain proteins on the cell’s surface, which helps the T cell identify the cell. If the surface proteins signal that the cell is normal and healthy, the T cell leaves it alone. If the surface proteins suggest the cell is cancerous or unhealthy in another way, the T cell starts an attack against it. Once T cells start an attack, the immune system begins to make more specialized proteins that prevent this attack from damaging normal cells and tissues in the body. These specialized proteins that keep healthy cells and tissues safe are called immune checkpoints.
Immune checkpoint inhibitors target these immune checkpoint proteins and help the immune system recognize and attack cancer cells. Immune checkpoint inhibitors essentially take the brakes off the immune system by blocking checkpoint inhibitor proteins on cancer cells or on the T cells that respond to them.
For example, PD-1 is a checkpoint protein on T cells. PD-L1 is another checkpoint protein found on many healthy cells in the body. When PD-1 binds to PD-L1, it stops T cells from killing a cell. Some cancer cells have a lot of PD-L1 on their surfaces, which stops T cells from killing these cells. Keytruda stops PD-1 from binding to PD-L1 and allows T cells to attack the cancer cells.
In 2020, the U.S. Food and Drug Administration (FDA) approved the combination of Keytruda and chemotherapy to treat unresectable locally advanced or metastatic triple-negative, PD-L1-positive breast cancer. Unresectable means the cancer can’t be removed with surgery. Based on the results of the KEYNOTE-522 study, the FDA has more recently approved the combination of Keytruda and chemotherapy before surgery, followed by Keytruda alone after surgery to treat early-stage triple-negative breast cancer with a high risk of recurrence (the cancer coming back).
Keytruda is given as an injection in a doctor’s office every 3 weeks or every 6 weeks, depending on the dose you’re receiving.
About the KEYNOTE-522 study
The ongoing KEYNOTE-522 study is looking to see if Keytruda can offer more benefits for early-stage triple-negative breast cancer than the standard of care, which is chemotherapy.
Earlier results from the KEYNOTE-522 study showed that the combination of Keytruda and chemotherapy before surgery for early-stage triple-negative breast cancer led to a better “pathologic complete response” than chemotherapy alone. “Pathologic complete response” means there are no active cancer cells present in tissue removed during surgery.
The study includes 1,174 women diagnosed with early-stage triple-negative breast cancer. The researchers randomly assigned the women in a 2:1 ratio to one of two treatments before surgery:
- 784 women were treated with chemotherapy and an injection of 200 milligrams (mg) of Keytruda every 3 weeks
- 390 women were treated with chemotherapy and a placebo injection that contained no medicine but looked just like Keytruda
The chemotherapy regimen for both groups was:
- four cycles of Taxol (chemical name: paclitaxel) plus carboplatin
- followed by four cycles of Adriamycin (chemical name: doxorubicin) or Ellence (chemical name: epirubicin) plus Cytoxan (chemical name: cyclophosphamide)
After the women had breast cancer surgery, they received nine cycles of either Keytruda or a placebo injection that looked just like Keytruda, but contained no medicine. This post-surgery treatment stopped for women who had a breast cancer recurrence or developed unacceptable side effects.
For this latest analysis, the researchers followed half the women for more than 3 years and half for shorter periods of time.
The 36-month event-free survival rate was:
- 84.5% for women treated with Keytruda and chemotherapy before surgery and Keytruda after surgery
- 76.8% for women treated with chemotherapy alone before surgery and a placebo injection after surgery
“These data support that pembrolizumab plus platinum-containing neoadjuvant chemotherapy, followed by adjuvant pembrolizumab after surgery, should be a new standard of treatment for patients with high-risk early-stage triple-negative breast cancer,” said lead author Peter Schmid, M.D., Ph.D., of Barts Cancer Institute at Queen Mary University of London, during his presentation.
If early-stage triple-negative breast cancer is high risk, it means it’s very likely that the cancer can come back, called recurrence by doctors.
The most common event was distant recurrence, which occurred in:
- 7.7% of women treated with Keytruda and chemotherapy
- 13.1% of women treated with chemotherapy alone
Of all the women in each treatment group:
- 77.1% of women treated with Keytruda and chemotherapy had moderate to severe side effects
- 73.3% of women treated with chemotherapy alone had moderate to severe side effects
What this means for you
The latest results from the KEYNOTE-522 study have led the FDA to approve Keytruda for the treatment of high risk, early-stage triple-negative breast cancer. Read about the FDA approval of Keytruda for early-stage triple-negative breast cancer.
If you’ve been diagnosed with early-stage triple-negative breast cancer and are deciding on treatments, you may want to talk to your doctor about this study. You also may want to ask if it’s possible to do PD-L1 testing on the cancer to see if you might benefit the most from a medicine like Keytruda. You also may want to ask about other trials looking at Keytruda and whether any of them might be a good fit for your unique situation.
Learn more about Immunotherapy, including how it works and possible side effects.
To talk with others about this study and immunotherapy, join the Breastcancer.org Discussion Board forum Immunotherapy - Before, During, and After.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser
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