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Pembrolizumab vs. nivolumab: how do they compare?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Nov 16, 2020.

Official Answer

by Drugs.com

Pembrolizumab (brand name: Keytruda) and nivolumab (brand name: Opdivo) are both prescription medications used to treat many different types of cancers, including solid tumors and blood cancers. They may be used alone or in combination with other medicines for cancers that are more advanced, have spread in the body, or are no longer responding to previous treatments.

Both pembrolizumab and nivolumab are in the class of medicines known as programmed death receptor-1 (PD-1) blocking antibodies (also called immune checkpoint inhibitors). They are targeted drug therapies that work by helping your immune system block the growth and spread of cancer cells in your body. They are not chemotherapy treatments.

For some types of cancer, these drugs may only be given only if your tumor has a specific genetic marker as determined by an FDA-approved test.

Pembrolizumab (Keytruda) is used treat certain types of cancer such as:

  • melanoma or Merkel cell carcinoma (types of skin cancer)
  • lung cancer
  • head and neck cancer
  • classical Hodgkin lymphoma
  • primary mediastinal large B-cell lymphoma
  • cancer of the kidney, bladder, and urinary tract
  • liver cancer
  • cancer of the cervix or uterus
  • advanced stomach cancer or esophageal cancer
  • triple negative breast cancer
  • a type of cancer that laboratory testing proves to have certain specific DNA mutations, including colorectal cancer.

Nivolumab (Opdivo) may be used to treat:

  • advanced melanoma (skin cancer)
  • lung cancer
  • kidney cancer
  • classical Hodgkin lymphoma
  • squamous cell cancer of the esophagus or squamous cell cancer of the head and neck
  • bladder cancer
  • liver cancer
  • a type of colorectal cancer that laboratory testing proves to have certain specific DNA mutations
  • malignant pleural mesothelioma

Which is better - pembrolizumab or nivolumab?

Only your doctor treating your cancer can answer this question. Cancer treatment is always individual, and what you may experience may be different from someone else.

The selection of your treatment will be determined based on your cancer type, overall medical condition, age, genetic markers, other treatments you are receiving, your preferences, insurance coverage and many other factors.

In general, PD-1 immune checkpoint inhibitors have been shown to significantly prolong overall survival (OS) in certain patients over a wide range of cancer types. But it’s important to know that cancer treatments do not work for everyone.

In clinical studies, researchers look at large groups of patients to better understand how well drugs work, how they compare, and how frequently side effects may occur. These results can help to inform you and your doctor which treatment might be best for you.

What do studies say about pembrolizumab or nivolumab?

Here are example study results from two cancer types, non-small cell lung cancer and melanoma. There are many other clinical studies looking at the effectiveness and safety of pembrolizumab and nivolumab in all their other approved uses. Always discuss the best cancer medication with your doctor, who knows your medical history and can recommend the best available treatment options for you.

Non-small cell lung cancer

Both pembrolizumab (Keytruda) and nivolumab (Opdivo) are used to treat non-small cell lung cancer (NSCLC) in different situations. Lab tests may need to be done on the cancer cells to show if they express certain proteins like PD-L1.

  • Pembrolizumab can be used alone or with chemotherapy as the first treatment for some patients with advanced or recurrent NSCLC. Recurrent cancer is cancer that returns after using other treatments.
  • Pembrolizumab is also used as initial treatment in patients with NSCLC that has not spread outside the chest and who cannot have surgery or radiation treatment.
  • Nivolumab can also be used as the first treatment in some patients with NSCLC. It is given along with ipilimumab (Yervoy), another immune checkpoint inhibitor, and may also be used with chemotherapy. It may be a treatment option for patients with advanced or recurrent lung cancer. Yervoy blocks CTLA-4, a different T cell protein.

Keytruda: In one study, 305 patients with advanced NSCLC received either pembrolizumab alone or a platinum chemotherapy regimen as a first treatment. Patients tested positive for the PD-L1 biomarker of at least 50%. These patients had no previous drug treatment and did not have an abnormal EGFR or ALK gene.

  • Results showed that more patients lived longer with the use of Keytruda compared to chemotherapy, 71% (110/154) of patients receiving Keytruda and 58% (87/151) of those on chemotherapy.
  • Keytruda also reduced the risk of the cancer spreading, growing or getting worse by 50% compared to chemotherapy.
  • Half of the patients on Keytruda were alive without their cancer spreading, growing, or getting worse at 10.3 months, compared to 6 months for patients on chemotherapy.

Opdivo + Yervoy: Patients received either pembrolizumab (Opdivo) + ipilimumab (Yervoy) or chemotherapy in a study of 793 previously untreated advanced NSCLC patients that tested positive for PD-L1.

  • After a follow-up of almost 30 months, pembrolizumab + ipilimumab reduced the risk of dying by 21% compared to using platinum-based chemotherapy.
  • At 17.1 months, half of patients using pembrolizumab + ipilimumab were alive, while at 14.9 months, half of patients on chemotherapy were alive.

Melanoma

Both pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs used to treat melanoma, a severe type of skin cancer. Nivolumab may be combined with another immunotherapy drug called ipilimumab (Yervoy).

They may be used to treat melanoma that is advanced, meaning it cannot be removed by surgery or it has spread in your body. They can also be used after surgery to lower the risk of cancer coming back. These treatments can help to shrink tumors and help you live longer.

Keytruda: In one clinical trial, pembrolizumab (Keytruda) was studied in patients with advanced melanoma and compared to ipilimumab (Yervoy), another immunotherapy medicine.

  • Pembrolizumab was shown to reduce the risk of dying by 31% compared to ipilimumab. Half of patients receiving pembrolizumab were alive without their cancer spreading, growing, or getting worse at 4.1 months, compared to 2.8 months for patients on ipilimumab.
  • At the time of follow-up, 185 of 277 patients (67%) treated with pembrolizumab were alive, compared to 166 of 278 patients (60%) treated with ipilimumab.
  • In addition, 33% of patients receiving pembrolizumab had their tumors shrink, compared to 12% of those receiving ipilimumab. Pembrolizumab reduced the risk of cancer spreading, growing, or getting worse by 42% compared to ipilimumab.

Opdivo + Yervoy or Opdivo alone: Opdivo used with Yervoy, and Opdivo used alone are both FDA-approved to treat advanced melanoma regardless of your BRAF test results.

BRAF is a gene involved in cell growth, and abnormal BRAF gene (called a BRAF + gene) can lead to cancer. However, your doctor may decide to test you for your BRAF results to help you decide on your treatment options.

One clinical study looked at 945 patients with advanced melanoma who had not previously been treated.

  • Patients received one of three treatments: either a combination of nivolumab (Opdivo) + ipilimumab (Yervoy), nivolumab (Opdivo) alone, or ipilimumab (Yervoy) alone.
  • In the group that received nivolumab (Opdivo) + ipilimumab (Yervoy), 52% of patients were alive at 5 years compared to 26% of patients receiving ipilimumab (Yervoy) alone. These results were similar to those seen previously at 28 months.
  • In patients who received nivolumab (Opdivo) alone, 44% of patients were alive at 5 years compared to 26% of patients receiving ipilimumab (Yervoy) alone.
  • In a follow-up analysis, half of patients who received nivolumab (Opdivo) + ipilimumab (Yervoy) went 11.5 months without their cancer growing, spreading or getting worse compared to 2.9 months for patients receiving ipilimumab (Yervoy) alone for melanoma.

How do side effects compare between these drugs?

In general, side effects of immunotherapy drugs can be similar and may include:

  • fatigue
  • cough
  • shortness of breath
  • headache
  • nausea
  • itching
  • skin rash
  • dizziness
  • loss of appetite
  • stomach pain
  • constipation
  • joint pain
  • diarrhea

More serious side effects can occur as well, although they may occur less frequently. These include:

  • infusion reactions that can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing.
  • autoimmune reactions where the immune system attacks other parts of the body. This can lead to serious or life-threatening problems in the lungs, intestines, liver, hormone glands, kidneys, skin, brain, or other organs.

Tell your doctor or nurse right away if you have any of these symptoms while you are receiving these medicines. For some serious side effects with immunotherapy, you may need to get high doses of corticosteroids to help slow down your immune system from overreacting.

If you are receiving other immunotherapy drugs or chemotherapy, your side effects may be different or more serious. Always discuss your expected treatment side effects with your doctor.

Visit here to review side effects in more detail:

How are pembrolizumab or nivolumab given?

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are given by a slow intravenous (IV) infusion into your vein, usually over at least 30 minutes. You will most likely receive this treatment in an outpatient clinic or hospital setting every 2, 3, 4 or 6 weeks, depending upon your treatment.

Your healthcare provider will give you this medicine. It is important you do not miss your appointments. The total amount of time you spend at the clinic will vary based on your treatment regimen. Your doctor or nurse can tell you what to expect.

Your doctor will determine the best dose and schedule for you based on the type of cancer or condition being treated, your weight, your age, other health conditions or treatments, and side effects that you experience, among other factors.

Most patients continue these medicines until their disease worsens or they have side effects that require them to discontinue treatment. In many cases, the treatments may be continued for up to 24 months. If you have serious side effects, your doctor may need to slow down or stop your treatment.

You will need medical or blood tests at the lab to check on the safety of this medication and if you can continue treatment. Your doctor will also check how well your liver and kidneys are working.

Which drug is more expensive?

  • According to the manufacturer, the list price* for one dose of pembrolizumab (Keytruda) given every 3 weeks is $9,869.94 and $19,739.88 when given every 6 weeks.
  • According to the manufacturer, the list price* for one dose of nivolumab (Opdivo) + ipilimumab (Yervoy) given for newly diagnosed advanced lung cancer is $21,583 and the $6,580 for nivolumab (Opdivo) given alone. Prices may vary for other uses.

*list prices current as of October 2020

Your cost for these medicines are based on if you have commercial (private) or government-sponsored insurance, your level of coverage, the administration and clinic fees, and other factors.

Most patients with insurance will not pay the list price but will pay a portion of the cost, known as a copay or coinsurance. Contact your insurance company to determine your specific cost for these medications, or ask your doctor or nurse for assistance.

The manufacturers (Merck for Keytruda and Bristol Myers Squibb for Opdivo) also have a co-Pay assistance program that may make your payments as low as $25 per medication or infusion. Contact them for additional information.

If you do not have insurance, or your insurance will not pay for these drugs, the pharmaceutical manufacturers may be able to help you get them affordably through various patient assistance programs.

This is not all the information you need to know about pembrolizumab (Keytruda) or nivolumab (Opdivo) for safe and effective use. Review the full product information, and discuss this information with your doctor or other health care provider.

References
  • Keytruda [product information]. Merck & Co. Whitehouse Station, NJ. Accessed Nov. 10, 2020 at https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf
  • Opdivo [product information]. Bristol Myers Squibb Co. Accessed Nov. 10, 2020 at https://packageinserts.bms.com/pi/pi_opdivo.pdf
  • Immunotherapy for Non-Small Cell Lung Cancer. American Cancer Society. Accessed Nov. 10, 2020 at https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/immunotherapy.html

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