Immunotherapy medicines use the power of your body’s immune system to attack cancer cells.
Cancer immunotherapy medicines work by helping your immune system work harder or more efficiently to fight cancer cells. Immunotherapy uses substances -- either made naturally by your body or man-made in a lab -- to boost the immune system to:
- stop or slow cancer cell growth
- stop cancer cells from spreading to other parts of the body
- be better at killing cancer cells
Keytruda (chemical name: pembrolizumab) is a type of immunotherapy known as an immune 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) versus “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. 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 surface, 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.
Keytruda is approved 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.
While there are no immune checkpoint inhibitors approved to treat breast cancer, doctors think that some, including Keytruda, may have potential.
A very early, very small study found that Keytruda combined with Herceptin (chemical name: trastuzumab) may offer benefits to people diagnosed with metastatic HER2-positive breast cancer with high levels of tumor infiltrating lymphocytes that has stopped responding to Herceptin.
The research was presented on Dec. 6, 2017 at the 2017 San Antonio Breast Cancer Symposium. Read the abstract of “Phase Ib/II study evaluating the safety and efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER2-positive metastatic breast cancer: Results from the PANACEA (IBCSG 45-13/BIG 4-13/KEYNOTE-014) study.”
Metastatic breast cancer, considered advanced-stage disease, is breast cancer that has spread to parts of the body away from the breast, such as the bones or liver.
Tumor-infiltrating lymphocytes (TILs) are white blood cells -- immune system cells -- that have left the bloodstream and moved into a cancer tumor. Because these immune system cells are already in the cancer tumor, researchers think that a cancer with high levels of TILs may be more responsive to immunotherapy medicines.
Both Herceptin and Keytruda are given intravenously, which means they’re delivered directly into your bloodstream through an IV or a port. A newer form of Herceptin, Herceptin Hylecta (chemical name: trastuzumab and hyaluronidase-oysk), can be given as an injection.
This study, called the PANACEA trial, combined two very early phases of clinical trials into one study. The phase Ib portion of the study looked to see if the combination of Keytruda and Herceptin was safe. The phase II portion of the study looked to see how effective the combination was. While the results of the PANACEA study were promising, much more research, including phase III trials, need to be done before Keytruda is regularly used to treat breast cancer.
The study included 58 people diagnosed with metastatic HER2-positive breast cancer that had become resistant to Herceptin:
- 46 of the cancers had high levels of PD-L1, called PD-L1-positive
- 12 of the cancers had low levels of PD-L1, called PD-L1-negative
Most of the people in the study had received other anti-HER2 medicines in addition to Herceptin:
- 42 people also had been treated with Kadcyla (chemical name: T-DM1)
- 17 people also had been treated with Perjeta (chemical name: pertuzumab)
- 26 people also had received other anti-HER2 medicines
The people in the study received 200 mg of Keytruda every 3 weeks in combination with the standard dose of Herceptin for 2 years or until the cancer grew.
None of the people had to reduce the dose of Keytruda or stop taking it because of side effects. So the phase Ib portion of the study concluded that Keytruda was safe.
Of the 46 PD-L1-positive cancers, seven had some response to the Keytruda-Herceptin combination, including two complete responses. A complete response means no cancer could be detected.
None of the 12 PD-L1-negative cancers had a response to the Keytruda-Herceptin combination.
When the researchers looked at just the PD-L1-positive cancers with 5% or higher levels of TILs, the response to the Keytruda-Herceptin combination were higher, suggesting that TIL levels may help identify people who will most benefit from this treatment combination.
“We wanted to investigate if immunotherapy approaches can work in patients with advanced HER2-positive breast cancer that is resistant to trastuzumab,” said Sherene Loi, M.D., Ph.D., associate professor at the Peter MacCallum Cancer Centre in Melbourne, Australia. “This proof-of-principle study suggests that immune evasion is a mechanism of resistance to trastuzumab and contributes to disease progression in advanced HER2-positive breast cancer. Our results suggest that PD-1 inhibition is likely to become part of the treatment armamentarium of HER2-positive disease in the future.”
Again, while the results of this study are encouraging, much more research needs to be done before immunotherapy medicines are regularly used to treat breast cancer.
For more information, visit the Breastcancer.org Immunotherapy section.
Editor’s Note: This article was updated with information about Herceptin Hylecta, which the FDA approved on Feb. 28, 2019.
On Nov. 13, 2020, the U.S. Food and Drug Administration approved Keytruda in combination with chemotherapy to treat unresectable locally advanced or metastatic triple-negative, PD-L1-positive breast cancer.
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