FDA Approval: Ramucirumab (Cyramza) for Stomach Cancer

What the FDA actually signed off on

On April 21, 2014, the FDA approved ramucirumab, sold as Cyramza, under biologics licence 125477 held by Eli Lilly. It was a priority review and a new molecular entity, and it carried orphan drug designation.

The 2014 label is specific about who it was for. Ramucirumab was cleared as a single agent for advanced gastric cancer, or adenocarcinoma of the gastro-esophageal junction, in people whose cancer had already been treated with fluoropyrimidine or platinum chemotherapy. That is second-line treatment, not a first option.

The drug is given as an infusion into a vein once every two weeks, with the amount worked out from body weight in the treatment unit.

How it works, in one paragraph

A tumor cannot grow past a few millimeters without building its own blood supply. It does that by releasing a signal called vascular endothelial growth factor, or VEGF, which docks onto a receptor called VEGFR2 on the cells lining nearby blood vessels. Those cells then sprout new vessels toward the tumor.

Ramucirumab is an antibody that plugs VEGFR2 so the signal cannot land. This is not chemotherapy and it does not attack cancer cells directly. It goes after the supply line.

The trial, and the size of the effect

The approval rested on one randomized trial, described in the label as Study 1. It enrolled 355 people with advanced gastric or gastro-esophageal junction cancer that had progressed after first-line chemotherapy. They were assigned two to one: 238 to ramucirumab plus supportive care, 117 to placebo plus supportive care. Neither patients nor doctors knew which was which. Median age was 60.

Median overall survival was 5.2 months with ramucirumab against 3.8 months with placebo. The hazard ratio was 0.78, and the p-value was 0.047. Median progression-free survival, the time before the cancer grew again, was 2.1 months against 1.3 months.

Read that plainly. The gain in median survival was about six weeks, and the survival result cleared the usual statistical bar by a narrow margin. It was still the first drug shown in a randomized trial to extend life in this setting after chemotherapy had failed. Our page on reading clinical trial results explains why a median is not a promise to any one patient.

The harms are on the label too

Cyramza carries a boxed warning, the FDA's strongest, for hemorrhage. The label states that the drug increased the risk of bleeding, including severe and sometimes fatal bleeds, and that it should be stopped permanently if severe bleeding occurs.

Other listed risks include arterial thromboembolic events, meaning clots such as stroke or heart attack, reported in 1.7% of the 236 treated patients in the trial. Severe high blood pressure occurred in 8% on the drug against 3% on placebo. Protein in the urine, a sign of kidney strain, appeared in 8% against 3%. Perforation of the bowel occurred in 0.8%. The most common side effects at any grade were high blood pressure and diarrhea.

People taking regular NSAIDs, such as ibuprofen, were kept out of the trial, so the bleeding risk in that group is unknown.

Where this sits in stomach cancer care

Ramucirumab is one line in a longer plan. NCI lists surgery as the main treatment: a subtotal gastrectomy removes the affected part of the stomach, a total gastrectomy removes all of it and joins the esophagus to the small intestine. Chemotherapy may come before surgery to shrink the tumor, or after it to lower the chance of return. Radiation is sometimes used. Other targeted drugs for stomach cancer now include trastuzumab, trastuzumab deruxtecan, regorafenib and zolbetuximab, chosen by what biomarker tests show.

The reason a second-line drug mattered so much is in the numbers. The American Cancer Society's projection for 2026 is 31,510 new US stomach cancer cases and 10,740 deaths, and SEER passes it along. What SEER itself measures, in people diagnosed between 2016 and 2022, is survival: 78.1% at five years when the cancer is still confined to the stomach, 39.0% once it has reached nearby lymph nodes, and 8.1% once it has spread further. Only 32% are found while still confined; 35% are already distant. Our page on stomach cancer treatment covers the sequence.

When to get checked

NCI lists early stomach cancer symptoms that look like ordinary indigestion:

• Indigestion or stomach discomfort that keeps returning
• Feeling bloated after eating
• Mild nausea, or losing your appetite
• Heartburn

And these, which NCI associates with more advanced disease:

• Blood in the stool, or stools that look black
• Vomiting, or trouble swallowing
• Stomach pain, or weight loss with no known cause
• Jaundice, meaning yellow eyes or skin
• A swollen abdomen from fluid buildup

Indigestion that has lasted more than three weeks, or that is new after age 50, is worth an appointment rather than another antacid. Our list of stomach cancer symptoms goes into more detail.

What this does not mean

• The approval covers advanced gastric or gastro-esophageal junction cancer already treated with chemotherapy. It says nothing about earlier-stage disease.
• A median survival of 5.2 months versus 3.8 months is a group result. Some people in the trial lived much longer, and some much shorter.
• An FDA approval means the evidence met the regulator's bar for a specific use. It is not a statement that the drug will help any given person.
• Labels change. The 2014 label quoted here is not the current one, and ramucirumab has since been approved in other settings.
• Whether this drug fits a particular person is a clinical decision that depends on the tumor, prior treatment and other conditions.

Sources

• FDA, CYRAMZA (ramucirumab) prescribing information, BLA 125477, approved 21 April 2014 — https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125477lbl.pdf
• FDA openFDA Drugs@FDA API record for BLA 125477 — https://api.fda.gov/drug/drugsfda.json?search=openfda.brand_name:%22CYRAMZA%22&limit=2
• NCI, Stomach Cancer Treatment — https://www.cancer.gov/types/stomach/patient/stomach-treatment-pdq
• NCI, Symptoms of Stomach Cancer — https://www.cancer.gov/types/stomach/symptoms
• SEER Cancer Stat Facts, Stomach Cancer — https://seer.cancer.gov/statfacts/html/stomach.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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