Opdivo (nivolumab) is immunotherapy, not chemotherapy. The two treatments work in fundamentally different ways: chemotherapy uses toxic drugs to kill rapidly dividing cells directly, while Opdivo works by helping your immune system recognize and attack cancer cells on its own. That said, Opdivo is frequently prescribed alongside chemotherapy, which is likely why the distinction gets confusing.
How Opdivo Works
Cancer cells are sneaky. They can hide from your immune system by displaying a protein on their surface that essentially tells immune cells to stand down. Opdivo blocks this interaction. Specifically, it attaches to a receptor called PD-1 on your immune cells, preventing cancer cells from flipping the “off switch” on your body’s natural defenses. Once that brake is released, your immune system can detect and fight the tumor.
This is the opposite of how chemotherapy works. Chemo drugs are toxic to any rapidly dividing cell, cancerous or not. They interfere with DNA replication or cell metabolism to kill cancer directly. That blunt approach is why chemo causes collateral damage to healthy cells in your gut lining, hair follicles, and bone marrow. Opdivo doesn’t poison cells. It reactivates your own immune response.
Why Opdivo Is Often Given With Chemo
Even though Opdivo itself is not chemotherapy, your treatment plan may include both. The FDA has approved Opdivo in combination with chemotherapy for several cancers, including resectable non-small cell lung cancer, advanced esophageal squamous cell carcinoma, gastric cancer, and urothelial carcinoma. The logic is straightforward: chemotherapy can quickly shrink tumors while immunotherapy trains the immune system to keep attacking cancer over time. Together, they hit the disease from two different angles.
In resectable lung cancer, this combination showed a meaningful benefit. At five years of follow-up, 65.4% of patients who received Opdivo plus chemotherapy before surgery were still alive, compared with 55% of patients who received chemotherapy alone. That translated to a nearly 30% reduction in the risk of death. Patients receiving the combination were also far more likely to have no detectable cancer remaining in the surgical specimen: 24% achieved a complete pathologic response versus just 2.2% with chemo alone.
Cancers Opdivo Treats
Opdivo has one of the broadest approval lists of any immunotherapy drug. It is FDA-approved for more than a dozen cancer types, sometimes as a standalone treatment and sometimes in combination with other drugs. The list includes:
- Melanoma (advanced or as follow-up treatment after surgery)
- Non-small cell lung cancer (before surgery with chemo, or for advanced disease)
- Kidney cancer (advanced, often combined with another immunotherapy or targeted therapy)
- Classical Hodgkin lymphoma (after other treatments have failed)
- Head and neck squamous cell carcinoma
- Bladder and urothelial cancer
- Colorectal cancer (specific subtypes with certain genetic features)
- Liver cancer
- Esophageal and gastric cancers
- Malignant pleural mesothelioma
In some of these cancers, Opdivo is used alone. In others, it’s paired with ipilimumab (Yervoy), another immunotherapy drug, or with standard chemotherapy regimens. Your oncologist chooses the approach based on the cancer type, stage, and specific tumor characteristics.
What Treatment Looks Like
Opdivo is given as an intravenous infusion that takes about 30 minutes. Depending on the dosing schedule, you’ll receive it either every two weeks or every four weeks. Treatment continues until the cancer progresses or side effects become unmanageable. Compared to a typical chemotherapy infusion, which can last several hours and may require pre-medications for nausea, Opdivo sessions tend to be shorter and simpler.
Side Effects Differ From Chemo
Because Opdivo revs up your immune system rather than poisoning fast-growing cells, its side effects look nothing like traditional chemo. You’re unlikely to experience the hair loss, severe nausea, or dangerously low blood counts that characterize chemotherapy. Instead, the risks come from your immune system becoming overactive and attacking healthy tissue.
These immune-related side effects can affect virtually any organ, but the most common involve the skin (rashes and inflammatory dermatitis), the gut (colitis, diarrhea), the liver (hepatitis), the thyroid (hypothyroidism), the lungs (pneumonitis), and the joints (inflammatory arthritis). Less common but still recognized are kidney inflammation, nerve damage, and pituitary gland dysfunction. Most of these are mild, but when they become severe, treatment is paused and immunosuppressant medications, typically steroids, are used to calm the inflammation.
Many patients find immunotherapy side effects more manageable than what they experienced on chemotherapy. Fatigue, a mild cough, or a skin rash can be easier to tolerate than the nausea, infections, and exhaustion that often accompany chemo. The tradeoff is that immune-related side effects can be unpredictable and occasionally affect organs you wouldn’t expect, so ongoing monitoring is important throughout treatment.
Speed of Response
One practical difference worth knowing: immunotherapy typically works more slowly than chemotherapy. Chemo can shrink tumors within days to weeks because it directly kills cancer cells. Opdivo needs time to “teach” your immune system to mount an effective response, which means visible results on scans may take longer. In some cases, tumors may even appear to grow briefly before the immune response kicks in, a phenomenon called pseudoprogression. This doesn’t mean the treatment isn’t working, but it does require patience and experienced interpretation of imaging results.
The potential payoff for that slower start is durability. Because immunotherapy creates a lasting immune memory against cancer cells, responses can persist for months or even years after treatment ends. Chemotherapy responses, by contrast, tend to fade once the drugs are stopped.