How is this drug name pronounced?
What cancer(s) does this drug treat?
Yervoy is approved for:
- Adult and pediatric patients 12 years of age and older with advanced melanoma that is metastatic (cancer has spread to other parts of the body from the original cancer site) or cannot be completely removed by surgery.
- Patients with skin melanoma that has been completely removed by surgery. In such cases, Yervoy is used to help keep melanoma from coming back.
Advanced kidney cancer
- Patients with previously untreated advanced renal cell carcinoma (kidney cancer) who are at moderate or high risk of their cancer getting worse. In such cases, patients are treated with Yervoy in combination with nivolumab (Opdivo).
Advanced colorectal cancer (MSI-H/dMMR)
- Adult and pediatric patients 12 years of age and older with colon or rectal cancer that has spread, have a tumor that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and have been treated with a fluoropyrimidine, oxaliplatin, and irinotecan, and the treatment did not work or stopped working. In such cases, patients are treated with Yervoy in combination with nivolumab (Opdivo).
Limitations of use:
Age: The safety and efficacy of Yervoy in patients under 12 years of age with advanced melanoma or with MSI-H/dMMR metastatic colorectal cancer have not been established. The safety and efficacy of Yervoy in patients under 18 years of age with advanced kidney or colorectal cancer have not been established.
Pregnancy/Breastfeeding: Yervoy can cause harm to a fetus, and is not recommended for use during pregnancy. Women who are able to become pregnant should use effective birth control during treatment and for at least 3 months after the last dose of Yervoy. The risks associated with Yervoy during breastfeeding are not known and cannot be ruled out; women are advised not to breastfeed during treatment and for 3 months after the last dose of Yervoy.
What type of immunotherapy is this?
- CTLA-4 blockade
How does this drug work?
- Target: CTLA-4
Yervoy is an antibody that attaches to a molecule called CTLA-4, which is present on the surface of T cells – the primary immune cells involved in the killing of cancer cells.
Before T cells can kill cancer cells, they first need to be “woken up”, or activated, and then they have to multiply to launch a potent attack. To help activate T cells, vigilant antigen-presenting cells patrol the body, pick up evidence of cancer, and travel to the lymph nodes to present this evidence to the T cells. If a particular T cell recognizes the evidence of cancer, it begins to wake up. However, to be fully activated for the cancer battle, T cells need a “caffeine” boost. This boost occurs when an activating molecule called CD28 on the surface of T cells interacts with molecules called CD80 or CD86 on the surface of antigen-presenting cells. However, shortly after the boost occurs, CTLA-4 shows up on the surface of T cells and competes with CD28 for the attention of CD80 or CD86, keeping the T cells from getting too much of the “caffeine” boost. Thus, CTLA-4 acts as a brake that keeps the T cells from creating an immune reaction that gets out of control, which could damage healthy tissues. Unfortunately, in cancer, the interaction between CTLA-4 and CD80/CD86 can prevent T cells from becoming activated enough to kill the cancer cells.
Yervoy binds to the CTLA-4 molecules on T cells in such a way that blocks the interaction between CTLA-4 and CD80/CD86, and allows the CD28 molecules on T cells to keep interacting with CD80/CD86 to fully activate the T cells, which is needed to attack cancer. Once the T cells are fully activated, they multiply to create a large army of potent T cells that can hunt down cancer cells throughout the body and kill them wherever they are found.
There may be other ways in which Yervoy helps destroy the cancer, and they are currently under investigation.
How is this drug given to the patient?
Yervoy is administered via a tube into a vein (intravenous infusion, or I.V.) over 30 or 90 minutes (depending on the dose and the type of cancer being treated). Yervoy is usually administered every three weeks for the first four doses. The frequency of subsequent dosing and the maximum number of doses depends on the cancer type. Administration of Yervoy does not require a hospital stay.
What are the observed clinical results?
It is important to keep in mind that each patient’s actual outcome is individual and may be different from the results found in the clinical studies. In addition, with immunotherapy, sometimes it takes several months for responses to be observed.
Advanced melanoma (metastatic or not removable by surgery)
In a clinical trial involving patients with previously treated melanoma that was metastatic or could not be removed by surgery, patients were treated with either Yervoy, an experimental cancer vaccine (gp100), or a combination of Yervoy and gp100. One year after treatment, 46% of patients treated with Yervoy alone were alive compared with 25% of patients treated with gp100. Two years after treatment, 24% of patients treated with Yervoy alone were alive compared with 14% of patients treated with gp100. The median overall survival with Yervoy or Yervoy plus gp100 was 10 months, compared to 6 months with gp100 alone. Six months after initiating treatment, 11% of patients treated with Yervoy alone, 6% of patients treated with Yervoy plus gp100, and 2% of patients treated with gp100 alone responded to their respective treatments.
Advanced melanoma (completely removed by surgery)
In a clinical study of patients with melanoma that was completely removed by surgery, 47% of patients treated with Yervoy remained melanoma-free three years after treatment, compared with 35% of patients who did not receive treatment.
Advanced kidney cancer (previously untreated)
In a clinical study of patients with previously untreated advanced kidney cancer, 42% of patients treated with a combination of Yervoy and nivolumab (Opdivo) responded to treatment, including 9% of patients whose tumor went away completely and 32% of patients who saw their tumors shrink. In contrast, 27% of patients responded to treatment with sunitinib (an oral chemotherapy). Two years after treatment, 67% of patients treated with Yervoy and Opdivo were alive, compared with 53% of patients treated with sunitinib. Among patients who responded to treatment, those treated with Yervoy and Opdivo responded for a longer time.
Advanced colorectal cancer (MSI-H/dMMR)
In a clinical study of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colon or rectal (“colorectal”) cancer, 49% of patients treated with a combination of Yervoy and Opdivo (nivolumab) responded to treatment, including 4% whose tumors disappeared completely and 45% who saw their tumors shrink. Additionally, 32% of patients treated with Opdivo alone responded to treatment, including 3% whose tumors disappeared completely and 30% who saw their tumors shrink. Of the patients who responded to the combination of Yervoy and Opdivo, 19% continued to respond for 12 months or longer. Of the patients who responded to Opdivo alone, 38% continued to respond for 12 months or longer.
What are the side effects?
The most common side effects of Yervoy include fatigue, diarrhea, nausea, vomiting, decreased appetite, belly ache, weight loss, itching, rash, headache, fever, and difficulty falling asleep or staying asleep.
Yervoy can cause the patient’s T cells to attack healthy cells throughout the body. Because of this, Yervoy can cause side effects that may involve any organ, can become serious or life-threatening, and may lead to death. Some of the serious side effects related to Yervoy include inflammation of the lungs, brain, liver (which can lead to liver failure), kidneys (which can lead to kidney failure), or colon (which can result in tears or holes in the intestine). Additionally, problems can arise with hormone glands (including thyroid, pituitary, and adrenal glands, as well as the pancreas), and nerves (which can lead to paralysis). Skin rash (which could become severe and life-threatening) and reactions related to the infusion may also occur. Patients should report any symptoms to their healthcare provider, who can then initiate actions to limit or reverse the side effects.
Patients may experience other side effects when Yervoy is used in combination with nivolumab (Opdivo). For a more complete list of possible side effects, see the full prescribing information.
FDA and EMA