Opdivo (Nivolumab): Uses, Actions, and Side Effects

What Should You Know About the Immuotherapy Drug Opdivo?

The immunotherapy drug Opdivo (nivolumab) is approved for treating several types of metastatic cancer (such as lung cancer, melanoma, and more), and has resulted in improved outcomes. The drug works by helping the body's own immune system eliminate cancer cells. Unlike chemotherapy, Opdivo specifically targets cancer cells and often has fewer side effects than traditional chemotherapy drugs. Common side effects include a rash, electrolyte abnormalities, and inflammation in a number of different organs. Let's look at the mechanism of action of Opdivo, when and how it may be used, potential side effects, and how healthcare providers are attempting to learn who will respond best to these drugs.

Microscopic organisms and vials
Istockphoto.com/Stock Photo©CIPhotos

Opdivo (Nivolumab)—Definition

Opdivo (nivolumab) is considered a type of immunotherapy drug, the first drug in this category approved for lung cancer (in 2015) and also now approved for several other cancers. Immunotherapy is a relatively new type of cancer treatment that uses the immune system to fight cancer.

There are many different types or categories of treatments that are classified as immunotherapy. Opdivo is in the category of checkpoint inhibitors.

Some people have had benefits from using Opdivo which were previously almost unheard of, even within the last decade. Opdivo does not work for everyone. Side effects are common, but in general, are milder than side effects found with many chemotherapy regimens.

Is Opdivo (Nivolumab) a Type of Chemotherapy?

Sometimes, the term chemotherapy is used loosely to describe any type of drug given to fight cancer. In this case, immunotherapy drugs may sometimes be referred to as chemotherapy.

Yet there are important differences The term "chemotherapy" usually refers to the use of drugs that affect cell division of all rapidly growing cells. The well-known side effects of chemotherapy arise because, in addition to fighting cancer cells, these drugs also affect normal cells that divide rapidly. It is this action of chemotherapy on healthy cells, such as those in the bone marrow (resulting in a low white count and more), hair follicles (resulting in hair loss), and digestive tract (resulting in nausea) that results in the common side effects.

In contrast, immunotherapy drugs are designed specifically to alter the body's immune system or use substances made by the immune system to fight cancer and do not attack all of the cells in the body. For this reason, immunotherapy drugs often have fewer side effects than traditional chemotherapy drugs.

How Opdivo (Nivolumab) Works (Mechanism of Action)

Opdivo (nivolumab) is an immunotherapy drug that is classified as a checkpoint inhibitor.

The mechanism of action of checkpoint inhibitors is easier to understand if you think of your immune system as a car, with checkpoint inhibitors being the brakes on the car. 

Our immune systems are designed to attack bacteria, viruses, and cancer cells in our bodies.

The immune system has checks and balances. These checkpoints serve to control the immune system so it doesn't underperform or overperform. An overactive immune system, for example, is a problem with autoimmune diseases such as rheumatoid arthritis and lupus.

Checkpoints and Cancer

The "brakes" that slow down the immune process are proteins referred to as checkpoints. The checkpoint proteins slow down the immune response so that it is not overactive. One of these proteins is PD-L1. PD-L1 binds to PD-1 receptors on T cells (the cells in the immune system most active in attacking cancer), telling them to be quiet.

Some cancer cells increase their production of PD-L1 molecules on their surface. When cancer cell PD-L1 binds to the PD-1 receptors on the T cells, it blocks the action of the immune system.

Opdivo, which is one of the checkpoint inhibitors FDA-approved to treat cancer, works by binding to and blocking the interaction between PD-1 by PD-L1. This essentially releases the brakes placed by the cancer cells on the immune system so that the body's immune system can fight cancer. All in all, Opdivo works by unblocking the immune system, so it can attack cancer cells.

Opdivo (Nivolumab) Uses

Opdivo is usually used for stage IV (inoperable) cancers, which cannot be treated with surgery and have usually spread to other parts of the body (referred to as metastatic).

What Cancers May Be Treated With Opdivo?

Opdivo (nivolumab) has been approved for the treatment of:

  • Lung adenocarcinoma (a type of non-small cell lung cancer)
  • Squamous cell carcinoma of the lungs (another type of non-small cell lung cancer)
  • Metastatic melanoma
  • Hodgkin disease
  • Head and neck cancer
  • Merkel cell carcinoma
  • Renal cell carcinoma (kidney cancer)

It is also being used in clinical trials for other cancers.

How is it Given?

Opdivo is given by intravenous injection over an infusion period of about an hour. It is usually given every 2 weeks.

Alone or in Combination

Opdivo may be given alone or in combination with other immunotherapy drugs, chemotherapy drugs, or radiation. Of note is that combination therapy may work well because chemotherapy or radiation therapy cause tumor cells to break down. The breakdown products of these cells are then "seen" by the immune system, which primes the system to help the immunotherapy drugs work better.

What Does “Durable Response” Mean?

A "durable response" refers to a long-lasting benefit of a drug on a tumor. There is not a specified time that defines durable response, but "long-lasting" usually means a minimum of 1 year and sometimes much longer.

If you see studies talking about a "durable response," this often contrasts with the typical type of response expected from chemotherapy. With stage IV solid tumors, chemotherapy can be effective but the tumor almost always becomes resistant to chemotherapy after a relatively short period of time (often defined in months). With targeted therapies, the response time is often longer, yet resistance often develops in a year's time depending on the particular drug, the type of cancer, and much more. Some of the newer targeted therapies appear to work longer than this.

A durable response does not mean a cure.

Immunotherapy May Continue to Work After Treatment is Done

Opdivo may continue to be effective after you stop taking it. With non-small cell lung cancer, some people have had durable responses even after discontinuing therapy.

What Are Studies and Clinical Trials Telling Us About Opdivo?

Studies have looked at the effect of Opdivo on specific cancers.

  • Non-small cell lung cancer: A 2017 review of nine studies involving people with stage III and stage IV non-small cell lung cancer found that nivolumab (and Tecentriq (atezolitumab) and Keytruda (pembrolizumab) improved overall survival more than chemotherapy when used second line (and also pembrolizumab first line in PDL-1 positive tumors). In addition, people experienced fewer side effects on the checkpoint inhibitors than on chemotherapy. Opdivo may be used for either lung adenocarcinoma or squamous cell carcinoma of the lungs. Opdivo should only be used for those people who do not have targetable gene mutations or haven't responded to targeted therapy.
  • Metastatic melanoma: Opdivo is now recommended first line (as the first treatment) for metastatic melanoma.
  • Metastatic small cell lung cancer
  • Esophageal cancer (unresectable, advanced, recurrent, or metastatic)
  • Classical Hodgkin lymphoma: Opdivo may used for people with classical Hodgkin lymphoma who are not improving after a stem cell transplant and use of targeted therapy.
  • Squamous cell head and neck cancer (metastatic or recurrent).
  • Renal cell carcinoma: Opdivo is approved both first line in combination with Yervoy(ipilimumab) and second line (after anti-angiogenesis inhibitor therapy) for advanced renal cell carcinoma, the most common type of kidney cancer.
  • Urothelial carcinoma: Opdivo is approved for people with this type of bladder cancer who are not improving on chemotherapy.
  • Merkel cell carcinoma
  • Colorectal cancer: One type of metastatic colon cancer after treatment with three chemotherapy drugs.
  • Hepatocellular carcinoma (liver cancer): Opdivo may be used after treatment with Nexavar (sorafenib).

When Does Immunotherapy Work Best?

The research on Opdivo and other immunotherapy drugs is still young, but with lung cancer at least, it seems that people who have smoked in the past are more likely to respond to the drug than those who have never smoked.

Tests to See if Opdivo May Be Effective

Tests that may be done to predict the response to Opdivo and other checkpoint inhibitors include:

  • PD-L1 levels: Tests for PD-L1 levels can, in some cases, predict a response to Opdivo, but the test has many limitations as far as deciding when to use the drug. Some people who have low levels of PD-L1 may still have a very strong response to the drug.
  • Tumor mutation burden: Tumor mutation burden is a biomarker test that looks at the number of mutations in cancer cells. Those who have a high tumor mutation burden (defined as more than 10 mutations per megabase on Foundation testing) are more likely to respond, but as with PD-L1 testing, there are exceptions, and it is still too soon to use the test as a method of choosing treatment.

Potential Side Effects Of Opdivo (Nivolumab)

Common side effects (those that occur in 10 percent or more of people) include:

  • Skin rash
  • Itching (pruritis)
  • Elevated potassium level (hyperkalemia) and low sodium level (hyponatremia)
  • Abnormal liver function tests such as ALT and alkaline phosphatase
  • Cough
  • Shortness of breath
  • Fatigue
  • Low white blood cell count
  • Muscle pain especially with lung cancer

Less common but serious adverse effects may include:

  • Inflammation, such as colitis (inflammation of the colon), pneumonitis (inflammation of the lungs), hepatitis (inflammation of the liver), nephritis (inflammation of the kidneys), pancreatitis (inflammation of the pancreas), and more
  • Eye conditions such as uveitis and dry eyes
  • Endocrine problems involving the thyroid gland, adrenal glands, and pituitary gland

Warnings While on Opdivo (Nivolumab)

People taking Opdivo should be monitored for inflammatory symptoms, and if present, the drug may need to be held or stopped. These include conditions such as pneumonitis, encephalitis, nephritis, and colitis. The drug can cause type I diabetes, and blood sugar should be monitored.

Adrenal insufficiency or adrenal fatigue can occur, and people should be aware of the potential of this condition as well as the possible symptoms.

Severe immune related rashes such as Stevens-Johnson syndrome may occur, and you should talk to your healthcare provider about any rashes you develop.

Overall, however, severe adverse reactions necessitating stopping the drug are uncommon, occurring less than 1 percent of the time. Make sure to talk to your oncologist about other potential symptoms as well as when you should call.

A Word From Verywell

Opdivo (nivolumab) is a very new drug that is classified as a type of immunotherapy. For those in whom these drugs are effective, we have sometimes seen responses of advanced solid tumors that were unimaginable just a few years ago. That said, they do not work for everyone, and we still do not have a good way of knowing who will respond best to treatment.

Side effects are common, especially symptoms such as a rash, itching, and thyroid dysfunction. Serious adverse reactions may sometimes occur as well. In general, however, Opdivo is tolerated better than traditional chemotherapy.

There has been much excitement from the medical community for a few reasons. Opdivo can be used to treat even very advanced solid tumors. In addition, it can be effective in several different types of cancer. It's likely that new uses for the drug will be approved in the near future, and many clinical trials are in progress assessing the effect of Opdivo on a wide variety of cancer types, both alone, and in combination with other treatments.

Frequently Asked Questions

  • What are the side effects of Opdivo?

    Common side effects of Opdivo (Nivolumab) can include an abnormal liver function test, cough, elevated potassium level, low sodium level, itching, skin rash, low white blood cell count, shortness of breath, and muscle pain (more frequent in lung cancer).

    Rare but serious side effects include eye conditions like uveitis and dry eyes, endocrine problems that involve the thyroid gland, adrenal gland, and pituitary glands, or many conditions and inflammation of different organs In the body. This can include hepatitis, colitis, pancreatitis, and more.

  • What is immunotherapy?

    Immunotherapy is a type of treatment that strengthens certain aspects of a person's immune system to help fight disease or infection. This is accomplished in multiple ways—by increasing the natural strength of the immune system, or by incorporating lab-produced substances that behave similarly to natural components of the immune system.Opdivo (Nivolumab) is one type of immunotherapy drug.

17 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. NCI. Nivolumab Receives Accelerated Approval from FDA for Advanced Liver Cancer. National Cancer Institute. National Institutes of Health.

  2. Chaudhari PB. Nivolumab - Pearls of EvidenceIndian J Med Paediatr Oncol. 2017;38(4):520–525. doi:10.4103/ijmpo.ijmpo_193_16

  3. Kato K, Cho BC, Takahashi M. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trialThe Lancet Oncology. 2019;20(11):1506-1517. doi:10.1016/s1470-2045(19)30626-6

  4. Guo L, Zhang H, Chen B. Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in TumorJ Cancer. 2017;8(3):410–416. doi:10.7150/jca.17144

  5. Baseri B, Samra B, Tam E, Chiu E, Leaf A. An Exceptional Responder to Nivolumab in Metastatic Non-Small-Cell Lung Cancer: A Case Report and Literature Review of Long-Term SurvivorsCase Reports in Oncological Medicine. 2019;2019:1-7. doi:10.1155/2019/1816472

  6. Kruger, S., Ilmer, M., Kobold, S. Advances in cancer immunotherapy 2019 – latest trendsJ Exp Clin Cancer Res 38, 268 (2019). doi:10.1186/s13046-019-1266-0

  7. Pons-Tostivint E, Latouche A, Vaflard P. Comparative Analysis of Durable Responses on Immune Checkpoint Inhibitors Versus Other Systemic Therapies: A Pooled Analysis of Phase III TrialsJCO Precision Oncology. 2019;(3):1-10. doi:10.1200/po.18.00114

  8. Malhotra J, Jabbour SK, Aisner J. Current state of immunotherapy for non-small cell lung cancerTranslational Lung Cancer Research. 2007;6(2):196-211. doi:10.21037/tlcr.2017.03.01

  9. Ellis PM, Vella ET, Ung YC. Immune Checkpoint Inhibitors for Patients With Advanced Non–Small-Cell Lung Cancer: A Systematic ReviewClinical Lung Cancer. 2017;18(5). doi:10.1016/j.cllc.2017.02.001

  10. Force J, Salama AK. First-line treatment of metastatic melanoma: role of nivolumabImmunotargets Ther. 2017;6:1–10. doi:10.2147/ITT.S110479

  11. Cooper MR, Almalki B, Willett KC. Nivolumab for the Treatment of Classical Hodgkin LymphomaJ Pharm Technol. 2017;33(6):237–244. doi:10.1177/8755122517716472

  12. Pirker R. Is smoking history the truly best biomarker for immune checkpoint inhibitor treatment in advanced non-small cell lung cancer?ESMO Open. 2018;3(5):e000421. doi:10.1136/esmoopen-2018-000421

  13. Teixidó C, Vilariño N, Reyes R, Reguart N. PD-L1 expression testing in non-small cell lung cancerTher Adv Med Oncol. 2018;10:1758835918763493. doi:10.1177/1758835918763493

  14. Alexander M, Galeas J, Cheng H. Tumor mutation burden in lung cancer: a new predictive biomarker for immunotherapy or too soon to tell?J Thorac Dis. 2018;10(Suppl 33):S3994–S3998. doi:10.21037/jtd.2018.09.35

  15. Zhou S, Khanal S, Zhang H. Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patientsTher Clin Risk Manag. 2019;15:211–221. doi:10.2147/TCRM.S193338

  16. Puzanov I, Diab A, Abdallah K. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working GroupJ Immunother Cancer. 2017;5(1):95. doi:10.1186/s40425-017-0300-z

  17. American Cancer Society. How Immunotherapy is Used to Treat Cancer.

Additional Reading
  • Postow, M., and J. Wolchok. Toxicities Associated With Checkpoint Inhibitor Immunotherapy. UpToDate.

  • Wang, X., Bao, Z., Zhang, X. et al. Effectiveness and Safety of PD-1/PD-L1 Inhibitors in the Treatment of Solid Tumors: A Systematic Review and Meta-Analysis. Oncotarget. 2017 May 31. (Epub ahead of print).

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."