FDA Approval: Regorafenib (Stivarga) for Colorectal Cancer

What the 2012 decision actually said

FDA approved Stivarga on 27 September 2012 under NDA 203085, held by Bayer. Drugs@FDA records it as a new molecular entity with priority review and orphan status.

The indication was narrow, and reading it tells you a lot. Stivarga was cleared for metastatic colorectal cancer. It was only for people already treated with three kinds of chemotherapy: fluoropyrimidine, oxaliplatin and irinotecan. They also had to have had an anti-VEGF drug. And, if the tumor was KRAS wild type, an anti-EGFR drug too.

In other words, it was for people who had run out of the standard options. That is the group the trial studied and the group the label describes.

The trial, with the numbers stated plainly

The label's clinical studies section describes one international, double-blind trial in 760 people with previously treated metastatic colorectal cancer. Participants were assigned 2 to 1: 505 received regorafenib plus best supportive care, 255 received placebo plus best supportive care.

Median age was 61. The median number of prior treatment lines for metastatic disease was three. Everyone had already had fluoropyrimidine, oxaliplatin, irinotecan and bevacizumab.

Median overall survival was 6.4 months on regorafenib against 5.0 months on placebo. The hazard ratio was 0.77 and the result was statistically significant.

That is a difference of about six weeks in the median.

Median progression-free survival was 2.0 months against 1.7 months. Tumors shrank enough to count as a response in 1% of the regorafenib group and 0.4% of the placebo group.

We are stating the numbers rather than the adjectives because a six-week median difference is a real finding and also a modest one. Both halves are true, and only one of them usually makes the headline.

What "median survival" is measuring

A median is the middle of a distribution. Half of the group did better than 6.4 months and half did worse. Some people in that trial lived considerably longer, and some considerably shorter.

A gap between two medians also does not mean each person gained six weeks. It means the whole curve moved. Our guide to cancer statistics explains how to read a figure like this. A group average is not a personal forecast.

What taking it involves

The dose is 160 mg by mouth once daily for the first 21 days of each 28-day cycle, taken with a low-fat breakfast. Fat content changes how much drug is absorbed, so the instruction is part of the dosing, not a courtesy. Take the amount your bowel team prescribed. The low-fat breakfast rule, though, applies to everyone on it.

That is the label's reference schedule. Many people start lower, so use the prescription your own bowel cancer team wrote.

The label carries a boxed warning, FDA's strongest, for liver injury. It states that severe and sometimes fatal hepatotoxicity has occurred in clinical trials, and it requires liver function testing before and during treatment.

The current label carries more warnings. They cover infection, bleeding, and a tear or abnormal opening in the gut. They cover skin toxicity, high blood pressure, and reduced blood flow to the heart. They also cover a brain condition called reversible posterior leukoencephalopathy syndrome, and poor wound healing. The drug should be held for at least two weeks before planned surgery.

Side effects reported in 20% or more of people include pain, hand-foot skin reaction, fatigue and diarrhea. The list also has reduced appetite, high blood pressure, infection, hoarseness, raised bilirubin, fever, mouth sores, weight loss, rash and nausea.

Hand-foot skin reaction is worth naming because it is common and it changes daily life: painful redness, thickening and peeling on the palms and soles.

Where this drug sits today

The label has grown since 2012. Stivarga now also covers gastrointestinal stromal tumor after imatinib and sunitinib, and hepatocellular carcinoma after sorafenib.

One detail in the colorectal indication has changed. The 2012 label said "if KRAS wild type." The current label says "if RAS wild-type." The reason is a decade of learning. Changes in related RAS genes, not only KRAS, predict that anti-EGFR drugs will not work.

What this does and doesn't change

For someone newly diagnosed with colorectal cancer, this approval changes nothing. It applies after several other treatments have been tried.

For someone who has used up those treatments, it added an option. In the trial, the other arm got supportive care alone. Six weeks of median survival against a hard set of side effects is a trade. Whether it is worth making is a personal judgment, not a medical fact.

Our overview of colorectal cancer covers the earlier stages of treatment, and targeted therapy explains what a kinase inhibitor does.

Where colorectal cancer stands

The American Cancer Society projects about 158,850 new colorectal cancer diagnoses in the United States in 2026 and about 55,230 deaths; SEER carries those projections. Median age at diagnosis is 66.

The stage figures below come from NCI's own registry data on people diagnosed between 2016 and 2022. Thirty-four percent of cases are found while confined to the bowel wall, with five-year relative survival of 91.3%. Thirty-seven percent have reached nearby lymph nodes, at 75.2%. Twenty-three percent are found after distant spread, at 16.9%. Across all stages the figure is 65.4%.

Those are registry averages for a whole population, not a statement about any one person.

What this story cannot tell you

• The trial enrolled people well enough to join a trial after three prior lines of treatment. That is a fitter group than everyone in the same spot.
• A statistically significant result is a statement about chance, not about size. This one was significant and small.
• Labels change. The indication wording moved from KRAS to RAS after the original approval, and the same page will read differently again in a few years.

Questions worth asking

• Where does this drug sit in the order of treatments for my situation?
• What does the trial evidence say about benefit and side effects for someone in my position?
• What liver monitoring will I need, and how often?

Sources

• FDA Drugs@FDA overview: STIVARGA (regorafenib), NDA 203085
• FDA label: STIVARGA, original approval 27 September 2012 (PDF)
• FDA label: STIVARGA, current prescribing information (PDF)
• FDA approval letter: STIVARGA, NDA 203085 (PDF)
• NCI SEER Stat Facts: Colorectal Cancer

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.

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