The immunotherapy medicine Keytruda (chemical name: pembrolizumab) along with chemotherapy offered better progression-free survival than chemotherapy alone as the first treatment for metastatic triple-negative breast cancer or triple-negative breast cancer that has come back (recurred) in the breast area but can’t be removed with surgery, with high levels of the PD-L1 protein, according to the KEYNOTE-355 study.
The research is part of the virtual program for the 2020 American Society of Clinical Oncology Annual Meeting. Read the abstract of “KEYNOTE-355: Randomized, double-blind, phase III study of pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer.”
Metastatic breast cancer is breast cancer that has spread to parts of the body away from the breast, such as the bones or liver.
Progression-free survival is how long a person lives without the breast cancer growing.
Keytruda is a type of immunotherapy medicine called a checkpoint inhibitor.
To start an immune system 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 these 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 a shield 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.
Immune checkpoint inhibitors target 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.
PD-1 is a type of checkpoint protein found 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 surface, which stops T cells from killing these cancer cells. An immune checkpoint inhibitor medicine that stops PD-1 from binding to PD-L1 allows T cells to attack the cancer cells.
Keytruda blocks the PD-1 pathway. Although it is not currently approved to treat breast cancer, Keytruda is used to treat advanced-stage skin cancer, certain types of non-small cell lung cancer, advanced-stage head and neck squamous cell cancer, Hodgkin lymphoma, advanced-stage urothelial cancer, and advanced-stage cancers with microsatellite instability-high or mismatch repair deficient, a specific type of genetic marker.
Keytruda is given as an injection, usually every 3 weeks.
About triple-negative breast cancer
Triple-negative breast cancer is:
So the growth of triple-negative disease isn’t driven by the hormones estrogen or progesterone or by the presence of too many HER2 receptors. This means that triple-negative breast cancer doesn’t respond to hormonal therapy (such as tamoxifen or an aromatase inhibitor) or therapies that target HER2 receptors, such as Herceptin (chemical name: trastuzumab), Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine), Nerlynx (chemical name: neratinib), Tykerb (chemical name: lapatinib), or Perjeta (chemical name: pertuzumab).
About 10% to 20% of breast cancers — more than one out of every 10 — are triple-negative. Triple-negative breast cancer tends to be more aggressive than other types of breast cancer.
Triple-negative breast cancer usually is treated with a combination of surgery, radiation therapy, and chemotherapy. Researchers are constantly working to find new medicines to treat triple-negative breast cancer.
About the KEYNOTE-355 study
The study included 847 people diagnosed with either:
- metastatic triple-negative breast cancer that had not been treated with chemotherapy yet
- triple-negative breast cancer that had come back in the breast area and could not be removed with surgery; these people had been considered disease-free for at least 6 months after treatment for the initial breast cancer
The researchers looked at whether the cancers had the PD-L1 protein on the surfaces of their cells, as well as how much PD-L1 was on the cells’ surface. Cancers that scored 10 or higher on the PD-L1 test were considered to have high levels of PD-L1. Cancers that scored 1 or higher were considered PD-L1-positive.
The people were randomly assigned to two treatment regimens:
- 566 people were treated with Keytruda every 3 weeks plus the researcher’s choice of one of three chemotherapy regimens: Abraxane (chemical name: albumin-bound or nab-paclitaxel), Taxol (chemical name: paclitaxel), or Gemzar (chemical name: gemcitabine)/carboplatin
- 281 people were treated with placebo (an injection that was just like Keytruda, but contained no medicine) plus the researcher’s choice of Abraxane, Taxol, or Gemzar/carboplatin
Follow-up time was about 17.5 months for people treated with Keytruda and chemotherapy and about 15.5 months for people treated with chemotherapy alone.
In people diagnosed with cancers with high levels of PD-L1, progression-free survival was:
- 9.7 months for people treated with Keytruda and chemotherapy
- 5.6 months for people treated with chemotherapy alone
This difference was statistically significant, which means that it was likely due to the difference in treatments and not just because of chance.
In people diagnosed with cancers that were PD-L1-positive, progression-free survival was:
- 7.6 months for people treated with Keytruda and chemotherapy
- 5.6 months for people treated with chemotherapy alone
This difference was not statistically significant, which means that the results could have been due to chance.
“There is a significant need for treatment regimens that can help women with metastatic triple-negative breast cancer, an aggressive disease,” said lead author Javier Cortes, M.D., of the IOB Institute of Oncology. “The results of this study demonstrate that if approved, Keytruda in combination with chemotherapy may offer certain women a new option for first-line treatment.”
Keytruda side effects
Like most cancer treatments, Keytruda can cause side effects, some of them severe. In the KEYNOTE-355 study, 96.3% of people treated with Keytruda and chemotherapy and 95% of people treated with chemotherapy alone had side effects.
Severe side effects (grade 3-5) were seen in 68.1% of people treated with Keytruda and chemotherapy and 66.9% of people treated with chemotherapy alone.
The most common severe side effects seen in people treated with Keytruda and chemotherapy were:
- low white blood cell counts
Side effects caused 18.1% of people treated with Keytruda and chemotherapy and 11% of people treated with chemotherapy alone to stop treatment.
Two people treated with Keytruda and chemotherapy died from treatment-related side effects.
Immune system-related side effects were seen in 25.6% of people treated with Keytruda and chemotherapy and in 6% of people treated with chemotherapy alone. The most common immune system-related side effect was hypothyroidism (underactive thyroid gland).
What this means for you
The results of the KEYNOTE-355 study are encouraging, and Merck, the company that makes Keytruda, is expected to ask the FDA to approve Keytruda to treat certain types of breast cancer.
Still, it’s important to know that these results are early results. The follow-up time is short — just over a year. Longer follow-up time will offer more information on how long cancers respond to Keytruda, as well as whether Keytruda improves overall survival — how long a person lives whether or not the cancer comes back.
If you’ve been diagnosed with metastatic triple-negative breast cancer or triple-negative breast cancer that has recurred in the breast area but can’t be removed with surgery and are deciding on treatments, you may want to talk to your doctor about this study. You may want to ask if a PD-L1 test can be done on the cancer to see if you might benefit from Keytruda, as well as about other trials looking at Keytruda and whether any of them might be a good fit for your unique situation.
For more information on immunotherapy medicines, how they work, and their possible side effects, visit the Breastcancer.org Immunotherapy pages.
To talk with others about these studies and immunotherapy, join the Breastcancer.org Discussion Board forum Immunotherapy - Before, During, and After.
Editor’s Note: On Nov. 13, 2020, the U.S. Food and Drug Administration (FDA) approved Keytruda in combination with chemotherapy to treat unresectable locally advanced or metastatic triple-negative, PD-L1-positive breast cancer. On July 26, 2021, the FDA approved Keytruda in combination with 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).
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser
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