FDA Approval: Crizotinib (Xalkori) for Lung Cancer

What was approved

The FDA approved crizotinib, sold as Xalkori, on August 26, 2011, under new drug application 202570. It was a Type 1 approval, meaning a new molecular entity, granted priority review with orphan status.

The indication on the original label is narrow and precise: treatment of patients with locally advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase positive, as detected by an FDA-approved test.

Three conditions have to hold at once. The cancer must be non-small cell lung cancer. It must be locally advanced or metastatic. And a validated test must show it is ALK-positive.

What ALK-positive means

ALK stands for anaplastic lymphoma kinase, a gene that makes a growth-signaling protein.

In a small share of lung cancers the ALK gene has broken and fused to a neighboring gene. The rearranged version produces a protein that is switched on permanently, telling the cell to keep dividing. Crizotinib blocks it.

This is targeted therapy in its literal sense. The drug does nothing useful in a lung cancer without the rearrangement, which is why the label ties the drug to the test. In Study A, ALK status was determined with the Vysis ALK Break-Apart FISH Probe Kit. Our page on biomarker testing explains how tumors are tested for changes like this.

The patient characteristics in the trials tell you something the label does not spell out. Median age was 52 in Study A and 51 in Study B — young for lung cancer, where SEER puts most diagnoses well past 65. And 68% and 72% of participants respectively had never smoked. ALK-positive lung cancer skews toward younger people and non-smokers.

The evidence behind the approval

Two multicenter, single-arm studies. Single-arm means nobody received a comparison treatment. Almost all participants had already had systemic therapy.

The primary measure in both was objective response rate — the share of people whose tumors shrank by a defined amount, judged against the RECIST criteria.

Study A, 136 patients. Median treatment duration 22 weeks. One complete response and 67 partial responses: an objective response rate of 50% (95% CI 42% to 59%). 79% of responses occurred within the first 8 weeks. Median duration of response was 41.9 weeks.

Study B, 119 patients. Median treatment duration 32 weeks. Two complete responses and 69 partial responses: 61% (95% CI 52% to 70%). 55% of responses occurred within the first 8 weeks. Median duration of response was 48.1 weeks.

The sentence the label puts in writing

Directly beneath the indication, the 2011 label states: "This indication is based on response rate. There are no data available demonstrating improvement in patient reported outcomes or survival with XALKORI."

That is unusually plain, and it is worth understanding rather than skipping. Tumors shrinking is not the same as people living longer or feeling better. The FDA accepted the response rate as sufficient to approve, while recording that the longer questions were unanswered at that point.

Dosing and side effects, from the label

The recommended dose was 250 mg by mouth twice daily, with or without food, continued as long as the patient was benefiting. Two smaller steps down were built into the label for people who could not tolerate the full amount. Those were label amounts from 2011. A prescription written for you now is what counts.

That was the approval-era reference amount. Anyone on crizotinib now should follow their current prescription.

The most common adverse reactions, affecting at least 25% of patients, were vision disorder, nausea, diarrhea, vomiting, edema, and constipation. Vision effects were prominent enough that the label carries specific patient counseling about them and about driving.

The label's warnings section covered pneumonitis — inflammation of lung tissue — abnormal liver blood tests, and QT interval prolongation, a change in the heart's electrical rhythm that matters most in people already predisposed to it.

Where lung cancer stands

The American Cancer Society projects 229,410 new United States lung and bronchus cancer cases in 2026 and 124,990 deaths, a projection SEER hosts rather than produces, making lung cancer the leading cause of cancer death at 20.0% of the total.

Five-year relative survival is 65.5% when found while confined to the lung, 38.2% once it has reached nearby lymph nodes, and 10.5% after spreading further. Only about 24% are caught at that first stage. Across all stages the figure is 29.5%.

Those survival figures are NCI's own SEER measurements, based on people diagnosed between 2016 and 2022 and pooling every subtype. They predate much of the targeted and immune treatment now in use and describe a group rather than a person.

When to get checked

Lung cancer screening has clear criteria: an annual low-dose CT scan for adults aged 50 to 80 with a 20 pack-year smoking history who smoke now or quit within the past 15 years.

But ALK-positive disease often appears in people who would never qualify. Symptoms matter regardless of smoking history. See a clinician for:

• A cough lasting more than three weeks, or a long-standing cough that changes in character.
• Coughing up blood, even once.
• Breathlessness on things you managed easily a few months ago.
• Chest or shoulder pain that persists.
• Hoarseness lasting beyond three weeks.
• Repeated chest infections.
• Unexplained weight loss or persistent fatigue.

Never having smoked does not rule out lung cancer, and it should not delay a chest X-ray. Our lung cancer page covers what happens after an abnormal scan.

What this approval cannot tell you

• Both supporting studies were single-arm. Without a control group there is no measurement of how crizotinib compared with the alternatives available in 2011.
• The label itself records that no survival or quality-of-life benefit had been demonstrated at approval.
• An approval defines eligibility in general terms. Whether it fits a particular person is a clinical decision that depends on their test result.
• This is the 2011 label. Indications, warnings, and dosing have been revised since, and newer ALK inhibitors now exist, so check current labeling rather than this summary.
• The drug is useless without the rearrangement it targets. Testing is not optional here; it is the gate.

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• U.S. Food and Drug Administration, XALKORI (crizotinib) prescribing information, original approval August 2011, NDA 202570: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202570s000lbl.pdf
• FDA Drugs@FDA overview for NDA 202570 (XALKORI): https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=202570
• SEER Cancer Stat Facts, Lung and Bronchus Cancer: https://seer.cancer.gov/statfacts/html/lungb.html
• U.S. Preventive Services Task Force, Lung Cancer: Screening: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening

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.

The National Cancer Information Foundation publishes Cancer Explained. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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