FDA Approval: Cabozantinib (Cabometyx) for Kidney Cancer

A second line, after the first one fails

Advanced kidney cancer had a standard opening move long before 2016: drugs that block VEGFR, a receptor tumors use to grow their own blood supply. They work, and then in most people they stop working.

The question was what to do next. On 25 April 2016 the FDA gave one answer, approving cabozantinib tablets as Cabometyx under NDA 208692 from Exelixis.

What cabozantinib blocks

Cabozantinib is an oral tyrosine kinase inhibitor. Kinases are proteins that relay growth signals inside a cell; this drug blocks several at once.

Its targets are VEGFR, plus two others called MET and AXL. That combination is the point. MET and AXL are implicated both in how metastatic renal cell carcinoma behaves and in how tumors become resistant to the first round of antiangiogenic drugs. Hitting them alongside VEGFR was a way to work past that resistance.

NCI describes the drug as blocking proteins that signal cancer cells to divide and proteins that signal the growth of new blood vessels feeding a tumor. Our overview of targeted therapy sets out how this class differs from chemotherapy.

What METEOR showed

The evidence came from METEOR, a randomized, open-label phase 3 trial published in the New England Journal of Medicine in 2015 and registered as NCT01865747.

It enrolled 658 people whose renal cell carcinoma had grown despite VEGFR-targeted treatment. They received either cabozantinib 60 mg daily or everolimus 10 mg daily, the drug that had been the usual next step.

Both amounts describe the trial arms. Your own kidney cancer team sets what you take, and dose changes during treatment are common.

Median progression-free survival, the time before the cancer grew again or the person died, was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower, with a hazard ratio of 0.58 and a confidence interval of 0.45 to 0.75. Tumors shrank measurably in 21% of the cabozantinib group against 5% on everolimus.

A planned interim look at overall survival favored cabozantinib, with a hazard ratio for death of 0.67, but it did not cross the boundary the trial had set for declaring that result at that point.

Doses had to be reduced in 60% of the cabozantinib group and 25% of the everolimus group. Roughly one in ten people in each group stopped treatment because of side effects. Our guide to clinical trial phases explains what a phase 3 comparison like this can and cannot settle.

The disease being treated

Renal cell cancer forms in the lining of the tiny tubes inside the kidney that filter blood and make urine. NCI notes that smoking and misuse of certain pain medicines affect the risk.

The American Cancer Society projects 80,450 new US kidney and renal pelvis cancer diagnoses and 15,160 deaths in 2026, a forecast SEER carries on its stat facts page. Five-year relative survival across all stages, for 2016 to 2022, is 79.2%.

Stage separates that sharply, over the same 2016–2022 diagnoses: 93.6% for localized disease still inside the kidney, 77.6% for regional disease reaching nearby tissue or nodes, and 20.3% for distant disease. About 15% of cases are distant at diagnosis, and that is the group METEOR studied. These are group averages from past years and describe no individual. More detail sits in our page on kidney cancer.

When to get checked

Kidney cancer is often quiet early on. NCI lists these as signs to raise with a doctor:

• Blood in the urine
• A lump in the abdomen
• Pain in the side that does not go away
• Loss of appetite
• Weight loss with no known cause

Visible blood in the urine warrants a same-week appointment even once, even if it clears. Other conditions cause all of these, which is a reason to have them checked rather than a reason to wait.

What this does and doesn't change

• METEOR's main measure was time without the cancer growing. The survival result was an interim look that did not meet its own threshold at that analysis.
• The approval is for advanced renal cell carcinoma after earlier antiangiogenic treatment. It says nothing about early kidney cancer, which is usually treated with surgery.
• Everolimus was the comparator. The trial does not rank cabozantinib against the immunotherapy combinations that came later.
• Most people needed a dose reduction. Real-world tolerability is part of the decision, not a footnote to it.
• The current label on DailyMed governs use, and it changes as new data arrive.

Sources

• New England Journal of Medicine (record via PubMed), Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma (METEOR) — https://pubmed.ncbi.nlm.nih.gov/26406150/
• FDA Drugs@FDA (openFDA API), CABOMETYX NDA 208692, original approval 25 April 2016 — https://api.fda.gov/drug/drugsfda.json?search=openfda.brand_name:%22CABOMETYX%22
• DailyMed, CABOMETYX (cabozantinib) label — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3850cce2-6137-42e5-a792-d318c4a4b3b5
• NCI, Cabozantinib-S-Malate — https://www.cancer.gov/about-cancer/treatment/drugs/cabozantinib-s-malate
• NCI PDQ, Renal Cell Cancer Treatment (Patient Version) — https://www.cancer.gov/types/kidney/patient/kidney-treatment-pdq
• SEER Cancer Stat Facts, Kidney and Renal Pelvis Cancer — https://seer.cancer.gov/statfacts/html/kidrp.html

How this article was prepared

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

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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