Keytruda vs. Opdivo: 5 Differences You Should Know About

If you watch television regularly, you’ve probably seen your fair share of Keytruda (pembrolizumab) and Opdivo (nivolumab) commercials. These medications are a type of immunotherapy called immune checkpoint inhibitors (ICIs). They allow your immune system to better see cancer cells and destroy them.

The commercials show people enjoying their favorite activities and promise a chance to live longer. And the claims have some backing: Immunotherapy has helped revolutionize the way we treat cancer. Many cancer types respond well to this type of treatment. In the last decade, more than 10 different ICIs have been FDA-approved for different types of cancer.

Here, we’ll discuss two commonly used ICIs, Keytruda and Opdivo, and see how they stack up.

1. Keytruda and Opdivo share some FDA-approved uses, but not all

Keytruda and Opdivo are gaining approvals for new uses (indications) at a dizzying rate. Keytruda is now approved for use in several unique types of cancer, while Opdivo is approved in many types, as well. Despite their shared FDA-approved indications, there are some slight differences between them. 

This chart shows their approved uses as of December 2023.

One other difference is that Keytruda is approved for use in multiple different cancers that have specific genetic changes (mutations). These include microsatellite-instability high (MSI-H), mismatch repair deficiency (dMMR), and tumor mutational burden-high cancers. Opdivo is only approved for use in people who have MSI-H or dMMR colon cancer.

Good to know: FDA approvals for Keytruda and Opdivo can be confusing. You may have to try certain medications first, have specific genetic changes, or use immunotherapy in combination with other medications in order to meet their criteria for use. Even if you see your cancer listed in the chart above, you should talk to your cancer specialist to see if immunotherapy is right for your situation.

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2. These injectable medications come in different dosages

Keytruda and Opdivo are both administered into your vein over a 30-minute period. But the amount of medication you’ll receive, and how often you’ll receive it, varies between the two.

In most adult cancers, Keytruda is given as a flat, 200 mg dosage every 3 weeks or a 400 mg dosage every 6 weeks. A weight-based, 2 mg per kilogram dosage every 3 weeks is more common for kids.

Opdivo’s possible dosages are a little more complicated. Options include:

• 240 mg every 2 weeks 

• 360 mg every 3 weeks

• 480 mg every 4 weeks 

• 3 mg/kg every 2 weeks (children who weigh less than 40 kg, or 88 lbs)

• 6 mg/kg every 4 weeks (children who weigh less than 40 kg)

• 1 mg/kg every 3 weeks, when used in combination with Yervoy (ipilimumab)

• 3 mg/kg every 2 to 3 weeks, when used in combination with Yervoy

The recommended dosages of Keytruda and Opdivo can vary based on cancer type, body weight, and use with other cancer medications. Many people prefer the longer dosing interval of every 4 to 6 weeks because they don’t have to visit a healthcare facility as often to receive the infusion. But your cancer specialist may start you on the lower, more frequent dosage first to make sure you can tolerate it.

3. Keytruda and Opdivo tend to be combined with different cancer treatments

Even though immunotherapy has changed the way we treat cancer, it’s not a perfect solution. Keytruda and Opdivo are often combined with chemotherapy to make your overall cancer treatment more effective. This is a common strategy for lung, stomach, and breast cancer.

Keytruda and Opdivo can also be combined with oral medications called tyrosine kinase inhibitors (TKIs). These medications interfere with signals that increase cancer cell growth. 

For instance, Keytruda can be used in combination with Lenvima (lenvatinib) or Inlyta (axitinib) for kidney cancer. Keytruda is also used with Lenvima in uterine cancer, while Opdivo has the option to be combined with a TKI called Cabometyx (cabozantinib) for kidney cancer.

One major difference between the two is that Keytruda isn’t usually combined with other ICIs. Only Opdivo can be combined with an ICI called Yervoy. This combination is commonly used for skin, kidney, and liver cancers, among others. 

4. The expected side effects are similar, but they’re not entirely the same

We mentioned that ICIs allow your immune system to find and destroy cancer cells. But sometimes ICIs can miss their target and attack healthy cells, too. This can lead to inflammation-related side effects in certain body parts, called immune-related adverse events (irAEs). These range from mild to life-threatening, but most are manageable if they are caught early.

Keytruda and Opdivo share many common irAEs. How frequently they happen changes based on your cancer type and if they’re combined with other cancer treatments. These irAEs include:

• Skin inflammation (dermatitis)

• Low thyroid function (hypothyroidism)

• Lung inflammation (pneumonitis)

• Gut inflammation (colitis)

• Liver inflammation (hepatitis)

In addition, the following side effects happen in up to 1 in 5 people who receive Keytruda or Opdivo as a single medication:

• Fatigue

• Muscle and bone pain

• Rash

• Itching

• Diarrhea 

• Fever

• Cough 

• Decreased appetite

• Shortness of breath

• Constipation

• Stomach pain

• Nausea or vomiting

The two medications do have some differences, too. Opdivo causes more back and joint pain, headache, and urinary or respiratory tract infections. Keytruda is more likely to cause low thyroid function. And although ICIs are commonly thought to have the same general side effects, a study suggests that Opdivo may cause more frequent and severe side effects compared to Keytruda. 

Regardless of which medication you’re receiving, make sure to reach out to your healthcare provider any time you’re experiencing a side effect that feels bothersome or concerning.

5. One is more widely used than the other

Keytruda is approved to treat more cancers than Opdivo. In addition, Keytruda has nearly 40 specific uses within those cancers. Opdivo has closer to 20. 

Keytruda is likely used more often than Opdivo because the higher number of indications allows more people to qualify for treatment.

Can you switch from Keytruda to Opdivo (or vice versa)?

In most cases, if Keytruda isn’t working for you, it’s unlikely that a switch to Opdivo will be beneficial. This is because they work so similarly. And the same goes for switching from Opdivo to Keytruda.

This isn’t always the case, though. It’s possible that your cancer specialist might switch you from Keytruda to Opdivo (or vice versa) if you have a side effect that you can’t tolerate. A recent case report found that heart inflammation was resolved by switching from Keytruda to Opdivo. Another case report revealed a successful switch to Keytruda in someone with an infusion reaction to Opdivo.

If you have a severe irAE with either medication, a more common strategy is to give you a break from treatment. You may also receive steroids such as prednisone or immunosuppressants such as infliximab (Remicade) to reverse the effects of the ICI. Depending on how severe your side effect was, you may be able to restart Keytruda or Opdivo with close monitoring. 

How to save on Keytruda and Opdivo

Keytruda and Opdivo are only available as reference (“brand-name”) medications. But GoodRx can help you navigate ways to save on your prescription.

• Save with a copay savings card. If you have commercial insurance and meet eligibility requirements, Keytruda’s price is as little as $25 per infusion if you use the manufacturer’s savings card. Opdivo’s price is as little as $0 per infusion if you use the manufacturer’s savings card.

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

Why trust our experts?

Written by:

Rachel Feaster, PharmD, BCOP, BCPS

Rachel Feaster has over 10 years of professional experience in ambulatory, inpatient, pharmacogenomics, and oncology care. She is board certified in oncology and pharmacotherapy.

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:

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.

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