Opdivo (nivolumab) is an immunotherapy drug used to treat at least 10 different types of cancer, including melanoma, lung cancer, kidney cancer, and bladder cancer. Rather than attacking cancer cells directly the way chemotherapy does, Opdivo works by helping your immune system recognize and destroy them. It’s given as an intravenous infusion, either alone or in combination with other treatments, depending on the type and stage of cancer.
How Opdivo Works
Cancer cells can evade your immune system by displaying a protein on their surface that essentially tells immune cells to stand down. Opdivo blocks that interaction. Specifically, it attaches to a receptor called PD-1 on your T cells (the immune cells responsible for hunting threats), preventing cancer cells from flipping the “off switch.” With that signal blocked, your T cells can recognize the tumor as a threat and mount an attack.
This is fundamentally different from chemotherapy, which kills fast-dividing cells indiscriminately. Because Opdivo works through the immune system, its side effect profile, response timeline, and the way it fights cancer all look distinct from traditional treatment.
Cancers Treated With Opdivo
The FDA has approved Opdivo for a wide range of cancers. In some cases it’s used as a first-line treatment, meaning it’s the initial therapy. In others, it’s used after a previous treatment has stopped working, or as an adjuvant therapy after surgery to reduce the risk of cancer coming back.
Melanoma
Opdivo treats melanoma that has spread or can’t be surgically removed, either on its own or combined with ipilimumab (Yervoy). It’s also used after surgery in patients whose melanoma had spread to lymph nodes or other sites, to help prevent recurrence. Long-term data shows that 44% of patients who received Opdivo after surgical removal of stage III or IV melanoma remained cancer-free at nine years.
Non-Small Cell Lung Cancer
This is one of the broadest areas of use for Opdivo. It’s approved for several different scenarios in non-small cell lung cancer (NSCLC): as a pre-surgery treatment combined with chemotherapy for tumors 4 cm or larger, as a first-line option for advanced disease (combined with ipilimumab, with or without chemotherapy), and as a single agent for patients whose cancer has progressed after platinum-based chemotherapy. For advanced NSCLC patients who had already failed prior treatment, 16% survived five years on Opdivo, roughly four times the rate expected with chemotherapy alone. Patients whose tumors had high levels of PD-L1 expression (50% or greater) fared even better, with a 43% five-year survival rate.
Kidney Cancer
For advanced kidney cancer (renal cell carcinoma), Opdivo is approved in combination with ipilimumab as a first-line treatment for patients with intermediate or poor-risk disease. It can also be used alone for patients whose cancer has progressed after previous therapy targeting the tumor’s blood supply.
Bladder and Urinary Tract Cancer
Opdivo treats urothelial carcinoma, the most common type of bladder cancer, in two settings. It can be given after surgery to patients at high risk of the cancer returning. It’s also used for locally advanced or metastatic disease that has progressed during or after platinum-based chemotherapy.
Head and Neck Cancer
For squamous cell carcinoma of the head and neck that has returned or spread, Opdivo is an option after platinum-based chemotherapy has failed.
Esophageal Cancer
Opdivo is used after surgery for esophageal or gastroesophageal junction cancer when there’s still residual disease following chemoradiation. It also treats advanced esophageal squamous cell carcinoma that has progressed after first-line chemotherapy.
Other Approved Cancers
- Malignant pleural mesothelioma: first-line treatment in combination with ipilimumab for tumors that can’t be surgically removed.
- Classical Hodgkin lymphoma: for patients whose disease has relapsed or not responded after a stem cell transplant and other treatments, or after three or more lines of therapy.
- Colorectal cancer: specifically for metastatic tumors that are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), which are genetic features that make tumors more responsive to immunotherapy. Used alone or with ipilimumab after standard chemotherapy has failed.
- Liver cancer (hepatocellular carcinoma): in combination with ipilimumab for patients previously treated with sorafenib.
Combination Therapy vs. Single Agent
Opdivo is frequently paired with ipilimumab (Yervoy), another immunotherapy drug that works through a different mechanism. While Opdivo blocks PD-1, ipilimumab blocks a separate immune checkpoint called CTLA-4. Using both together unleashes the immune system from two different angles, which can produce stronger anti-tumor responses. This combination is approved for melanoma, lung cancer, kidney cancer, mesothelioma, colorectal cancer, and liver cancer.
In some lung cancer settings, Opdivo is combined with both ipilimumab and a short course of chemotherapy. The chemotherapy helps kill enough cancer cells to release tumor proteins that the now-activated immune system can target. For kidney cancer, Opdivo may also be paired with cabozantinib, a targeted therapy, rather than ipilimumab.
What Treatment Looks Like
Opdivo is given as an IV infusion, typically over 30 to 60 minutes. The standard schedule is every two to four weeks, and treatment continues as long as the cancer responds or until side effects become unmanageable. For adjuvant use (after surgery), treatment generally lasts up to one year.
Response to immunotherapy can take longer to show up on scans than with chemotherapy. In some cases, imaging may initially suggest the tumor is growing before the immune response kicks in, a phenomenon called pseudoprogression. Your oncology team will use repeat scans to distinguish true progression from an immune response that’s still building.
Common Side Effects
Because Opdivo revs up the immune system, its side effects largely stem from that same immune system overreacting and attacking healthy tissue. These are called immune-related adverse events, and they can affect virtually any organ.
Skin reactions are the most frequent, with rash and itching reported in up to 71% of patients on checkpoint inhibitor therapy. The vast majority are mild. Diarrhea affects up to 19% of patients on Opdivo alone, though rates are higher when it’s combined with ipilimumab. Joint and muscle pain occur in up to 40% of patients. Fatigue is also very common.
More serious but less frequent reactions include inflammation of the lungs (pneumonitis), occurring in about 3% of patients on Opdivo alone and up to 10% with combination therapy. Liver inflammation occurs in 2% to 10% of patients on a single agent, jumping to 25% to 30% with the Opdivo-ipilimumab combination. Hormone-producing glands, particularly the thyroid and pituitary, can be disrupted in roughly 10% of patients, sometimes requiring long-term hormone replacement.
Severe side effects (grade 3 or 4) are uncommon with Opdivo alone. Skin toxicity reaches grade 3 or higher in 3% or fewer patients on monotherapy. Kidney injury at grade 3 or 4 occurs in less than 1% on a single agent. Neurological side effects of any grade affect about 6% of patients on Opdivo, with severe cases under 1%. Combination therapy raises all of these rates, which is why oncologists weigh the added benefit against the added risk for each patient’s specific cancer.
PD-L1 Testing and Eligibility
For some cancers, particularly certain lung cancer indications, your tumor may need to express PD-L1 at a certain level (1% or higher) before Opdivo is prescribed. This testing helps predict whether the drug is likely to work. However, PD-L1 testing is considered complementary, not mandatory, across most Opdivo indications. Many approved uses don’t require any specific biomarker. For colorectal cancer, the relevant test is for microsatellite instability or mismatch repair status rather than PD-L1.
Your oncologist will determine the right testing based on your cancer type and treatment history. Some patients with low or undetectable PD-L1 still respond to Opdivo, which is part of why the testing requirement varies by indication.