What Are Opdivo and Yervoy — and Why Are They Taken Together?

Opdivo (nivolumab) and Yervoy (ipilimumab) are medications used to treat certain types of cancer. You may have already heard of Yervoy and its breakthrough success in treating an advanced type of skin cancer called melanoma. 

Historically, melanoma was a difficult cancer to treat with traditional chemotherapy treatments. This changed when Yervoy came along as a type of cancer immunotherapy. And after Yervoy, other types of cancer immunotherapy medications — like Opdivo and Keytruda (pembrolizumab) — also emerged. 

These medications are now used as effective treatment options for many different types of cancer. Opdivo and Yervoy can also be used together. They complement one another — bettering their effectiveness against cancer cells. 

Here, we’ll discuss how Opdivo and Yervoy work, how effective they are, and some side effects to be aware of.

What are Opdivo and Yervoy?

Opdivo (nivolumab) is a brand name medication used to treat certain types of cancer. This includes melanoma, lung cancer, bladder cancer, and other types of cancers. Opdivo is a biologic medication. More specifically, it’s a type of immunotherapy. It’s given as an intravenous (IV) infusion over a period of time. This means it’s given into your vein. 

Yervoy (ipilimumab) is a brand name medication that is also used to treat certain types of cancer. It’s also sometimes given in combination with Opdivo. Yervoy is also a biologic medication that is an immunotherapy. Yervoy can treat cancers such as skin cancer, lung cancer, and kidney cancer. Yervoy is also given as an IV infusion.

Why are Opdivo and Yervoy taken together?

These two medications may be used alone or with other cancer treatments. But they’re also commonly given together. In fact, Opdivo and Yervoy are FDA-approved to be given together to treat the following cancers:

• Melanoma (a type of skin cancer)

• Advanced renal cell carcinoma (a type of kidney cancer)

• Metastatic non-small cell lung cancer (an advanced type of lung cancer)

• Certain types of colorectal cancer

• Malignant pleural mesothelioma (a type of cancer that affects a lining that surrounds many internal organs)

• Hepatocellular carcinoma (a type of liver cancer)

How do Opdivo and Yervoy work?

Opdivo is an immunotherapy medication, meaning it helps your body's immune system better fight cancer. Opdivo is in a class of medications called PD-1 inhibitors, also known as immune checkpoint inhibitors. 

PD-1 is an immune checkpoint protein found on immune cells called T cells. Immune checkpoint proteins help keep the immune system in check. In other words, they can tell the immune system to rest, or to not be active. When PD-1 is activated, cancer cells can hide from T cells and stop the T cells from killing the cancer cells.

Opdivo works by blocking the PD-1 receptor. This unleashes T cells in the immune system to better detect and kill cancer cells.

Yervoy is also an immunotherapy medication, but it works differently than Opdivo. Yervoy binds to a different immune checkpoint protein. It binds to cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) proteins on T cells in the immune system. 

When activated, CTLA-4 allows the cancer to evade detection from the immune system. When Yervoy blocks CTLA-4, the immune system is more active and ready to fight cancer cells.

Opdivo and Yervoy target two different immune checkpoints — PD-1 and CTLA-4 — to better fight cancer cells. Yervoy helps T cells spread and be more active. Meanwhile, Opdivo helps T cells better recognize cancer cells. They work together in complementary ways.

How effective are Opdivo and Yervoy?

Medication effectiveness is different for everyone. There are some studies that try to quantify medication effectiveness, but true effectiveness may be different. It depends on your cancer, other health conditions you may have, and other medications you might be receiving.

Regardless, some statistics are available as examples. 

Opdivo, in combination with Yervoy, is FDA-approved as a first-choice treatment for adults with metastatic non-small cell lung cancer (NSCLC) whose tumors have PD-L1 and don’t have abnormal EGFR or ALK genes. PD-L1 is a protein found on lung cancer cells. If a cancer has PD-L1, this means there’s a good chance your cancer will respond to immunotherapy. 

In a clinical trial of almost 800 people with metastatic NSCLC, Opdivo and Yervoy together reduced the risk of dying by over 20% compared to standard chemotherapy. And after 4 years, 29% of people who received both Opdivo and Yervoy were alive compared to 18% who received standard chemotherapy. In other words, people who received Opdivo and Yervoy lived longer than people who didn't.

The combination of Opdivo and Yervoy is an effective treatment for other types of cancer, such as melanoma and kidney cancer. But, again, success rates vary.

What are common side effects of Opdivo and Yervoy?

Opdivo and Yervoy can cause mild to serious side effects. They can cause the immune system to attack healthy cells, causing immune-related side effects like skin rashes or severe diarrhea. Side effects can occur during or after treatment, and may worsen over time. And when Opdivo and Yervoy are given in combination together, the risk of side effects may be higher. 

Other common side effects of Opdivo and Yervoy include:

• Feeling tired

• Muscle or joint pain

• Shortness of breath

• Fever

• Nausea 

• Low thyroid hormone levels

Are there any more serious risks or side effects?

Serious side effects can be managed and treated if caught early, but may result in needing to stop treatment if they become too severe.

Serious side effects of Opdivo and Yervoy may include:

• Lung problems: Cough, chest pain, shortness of breath

• Stomach problems: Diarrhea, severe stomach pain, weight loss

• Liver problems: Nausea and vomiting, right sided pain, yellow skin or eyes

• Hormone gland problems (like thyroid, adrenal, and pancreas): Headaches, extreme tiredness, mood changes

• Kidney problems: Less urine than normal, blood in urine, swelling in ankles

• Skin problems: Rash, skin blistering, itching

• Brain inflammation: Headache, confusion, memory problems

• Problems in other organs: Changes in eyesight, muscle and joint pain, muscle weakness

• Infusion reactions: Skin flushing and itching during or after an infusion

If you’re experiencing symptoms like these, it’s recommended to reach out to your cancer specialist for guidance right away. 

How to save on Opdivo and Yervoy

Opdivo and Yervoy are only available as brand-name medications. But GoodRx can help you navigate ways to save on your prescription.

• Save with patient assistance programs. If you’re uninsured or underinsured, you may be eligible for the Opdivo and Yervoy patient assistance programs, which offer the medications at no charge.

• Save with a copay savings card. If you have commercial insurance and meet eligibility requirements, Opdivo and Yervoy’s price is as little as $0 if you use the manufacturer’s savings card.

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Written by:

Sonja Jacobsen, PharmD, BCPS, BCOP

Sonja Jacobsen, PharmD, BCPS, BCOP,  is a clinical oncology pharmacy specialist currently practicing in Seattle. She has been practicing as a pharmacist since 2015 and is licensed to practice in Washington state and North Carolina.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

John Strickler, MD

John Strickler, MD, joined the Duke University faculty in 2011 and is now an associate professor of medicine in the division of medical oncology. His research focuses on precision cancer medicine: identification of genomic biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy.

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