CheckMate 214: What the Kidney Cancer Trial Found

Two immune drugs against one targeted drug

Before 2018, first treatment for advanced kidney cancer usually meant sunitinib. It is a tyrosine kinase inhibitor, a tablet that cuts off the blood supply a tumor builds for itself.

CheckMate 214 tested something different: two immunotherapy drugs given together, nivolumab and ipilimumab. The results, published in the New England Journal of Medicine in 2018, changed first-line treatment for a large part of this disease.

How the two drugs differ from each other

Both are checkpoint inhibitors, but they release different brakes.

Nivolumab blocks PD-1, a switch on T cells that tumors use to shut those T cells down inside the tumor itself.

Ipilimumab blocks CTLA-4, a different switch that acts earlier, in the lymph nodes, where T cells are first activated.

Releasing both brakes produces a stronger immune response than either alone. It also produces more immune side effects, because the same brakes keep the immune system off healthy tissue. Our overview of immunotherapy explains that trade-off.

Who took part, and the risk groups

A total of 1,096 adults with previously untreated advanced clear-cell renal cell carcinoma were randomly assigned. 550 received nivolumab plus ipilimumab, and 546 received sunitinib.

Not everyone was in the group where the main questions were tested. Kidney cancer uses a risk classification built from things like blood counts, calcium level, performance status, and how long ago the cancer was diagnosed. It sorts people into favorable, intermediate, and poor risk.

The primary analysis covered the intermediate- and poor-risk patients: 425 in the immunotherapy arm and 422 on sunitinib. That is 847 of the 1,096.

What the trial found

At a median follow-up of 25.2 months in the intermediate- and poor-risk group:

• 75% of the immunotherapy group were alive at 18 months, with a 95% confidence interval of 70 to 78. On sunitinib the figure was 60%, with an interval of 55 to 65.
• Median overall survival had not been reached with nivolumab plus ipilimumab. With sunitinib it was 26.0 months. The hazard ratio for death was 0.63.
• Tumors shrank meaningfully in 42% of the immunotherapy group and 27% on sunitinib.
• Complete response, meaning no detectable cancer left, occurred in 9% versus 1%.

One result did not go the way the headline suggests. Median progression-free survival was 11.6 months against 8.4 months, with a hazard ratio of 0.82 and a p-value of 0.03. The trial had set its own significance threshold for that endpoint at 0.009, so this did not meet it.

Side effects went in an unexpected direction. Severe treatment-related side effects, grade 3 or 4, were less common with immunotherapy, at 46% against 63%. But more people stopped treatment because of side effects on immunotherapy, 22% against 12%.

Why the side-effect picture is not straightforward

Sunitinib produces a steady, predictable set of problems: fatigue, hand-foot syndrome, high blood pressure, mouth sores. They are common, and they last as long as the drug does.

Immune side effects behave differently. They are less frequent but can hit any organ, arrive without warning, and sometimes require steroids or permanent discontinuation. Colitis, hepatitis, pneumonitis and thyroid or pituitary problems are all on the list.

That is why fewer severe events and more discontinuations can both be true at once.

When to get checked

There is no screening program for kidney cancer in people at average risk. Many kidney cancers are found by accident, on a scan done for something else entirely.

See a clinician if you notice:

• Blood in the urine, even once, even if it clears. Visible blood in the urine always needs assessment.
• A persistent ache or mass in the side or lower back on one side.
• Unexplained weight loss, or fever with no infection to explain it.
• Anemia found on a blood test with no clear cause.

Blood in the urine is the one that gets ignored most often, because it can come and go. A single episode is enough reason for an appointment.

Tell your clinician if kidney cancer runs in your family, or if you have von Hippel-Lindau syndrome or another inherited condition affecting the kidneys. Our page on kidney cancer covers how the diagnosis is made.

What this trial cannot tell you

• It covers previously untreated advanced clear-cell kidney cancer. Other kidney cancer types were not studied here.
• The main results were tested in the intermediate- and poor-risk group, not in favorable-risk patients.
• Progression-free survival did not meet the trial's own threshold for significance.
• Median follow-up was 25.2 months. That is a snapshot, not a lifetime.
• The first-line landscape has continued to change since 2018, so this is one important step rather than the current standard in full. Clinical trial phases explains what a phase 3 trial does and does not settle.

The wider picture

The American Cancer Society projects about 80,450 new kidney and renal pelvis cancer diagnoses in the United States in 2026, and about 15,160 deaths, a projection SEER carries beside its own measurements. Five-year relative survival across all stages was 79.2% for 2016 to 2022. About 66% of cases are found while still confined to the kidney, and 15% are already distant.

NCI notes that renal cell cancer can often be cured when it is found while still localized to the kidney and the tissue immediately around it, and that the chance of cure relates directly to stage.

These figures describe a population over past years of care. They are not a prediction for any individual, and the group CheckMate 214 studied sits at the harder end of that distribution.

Sources

• Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med 2018;378:1277-1290
• ClinicalTrials.gov record for NCT02231749
• NCI PDQ: Renal Cell Cancer Treatment (Health Professional Version)
• SEER Cancer Stat Facts: Kidney and Renal Pelvis Cancer

How this page was made

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

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