PROFILE 1014: What the Lung Cancer Trial Found

What ALK-positive means

ALK stands for anaplastic lymphoma kinase. It is a gene, and in a small share of non-small cell lung cancers a piece of it has fused to a neighboring gene. The fused version makes a protein that tells the cell to keep dividing.

Lung cancers carrying that fusion are called ALK-positive. They are found by testing tumor tissue, not by a scan or a symptom. NCI lists ALK alongside EGFR as one of the gene changes checked when planning treatment for non-small cell lung cancer.

Crizotinib is a drug that blocks the ALK protein. By 2010 it was known to work in people whose cancer had already progressed on chemotherapy. PROFILE 1014 asked a different question: should it come first?

How the trial was built

It was an open-label phase 3 trial in 343 people with advanced ALK-positive non-squamous non-small cell lung cancer. None had received systemic treatment for advanced disease.

Half were assigned crizotinib, 250 mg by mouth twice a day. That was the study's set amount. Anyone taking crizotinib should follow their own prescription. Half were assigned intravenous chemotherapy: pemetrexed plus either cisplatin, both worked out from body size, or carboplatin dosed to a target exposure, every three weeks for up to six cycles.

Crizotinib is a tablet taken at home. If it is part of your treatment, the amount on your own prescription is the one to follow.

People on chemotherapy could cross over to crizotinib if their cancer grew.

The primary endpoint was progression-free survival, judged by independent radiologists rather than by the treating doctors. That detail matters in an open-label trial, where everyone knows who is taking a pill and who is sitting in an infusion chair.

The results

Progression-free survival was longer with crizotinib: a median of 10.9 months against 7.0 months. The hazard ratio for progression or death was 0.45, with a 95% confidence interval of 0.35 to 0.60 and a p-value below 0.001.

Tumors shrank in 74% of the crizotinib group against 45% on chemotherapy.

Overall survival is where the picture gets more complicated. Median survival was not reached in either group, meaning fewer than half the people in each had died when the analysis was done. The hazard ratio for death was 0.82, with a confidence interval of 0.54 to 1.26 and a p-value of 0.36. That interval crosses 1, so the trial did not show a survival difference.

One-year survival was 84% with crizotinib and 79% with chemotherapy.

The report also found something that trials often skip: compared with chemotherapy, crizotinib produced a greater reduction in lung cancer symptoms and greater improvement in quality of life.

Side effects, by kind rather than by count

The two arms did not just differ in how many side effects they caused. They differed in what kind.

The most common problems with crizotinib were vision disorders, diarrhea, nausea, and swelling. With chemotherapy they were nausea, fatigue, vomiting, and loss of appetite.

Vision disorders are worth naming because people do not expect a lung cancer drug to affect sight, and so may not mention it. Anything new about vision belongs in the conversation with the oncology team.

Reading a crossover trial

Anyone on chemotherapy whose cancer grew could switch to crizotinib. That is the ethical choice and it makes the survival comparison hard to interpret, because the control group ends up receiving the study drug too.

So the honest summary is narrow. Starting with crizotinib delayed progression, shrank more tumors, and made people feel better than starting with chemotherapy. It did not, in this analysis, show that people lived longer.

Our explainer on clinical trial phases covers why the endpoint a trial chooses shapes what it can prove.

When to get checked

Lung cancer often causes nothing early. It is sometimes found on a chest x-ray taken for another reason. NCI says to check with a doctor about:

• Chest discomfort or pain.
• A cough that does not go away or gets worse over time.
• Trouble breathing, or wheezing.
• Blood in sputum, the mucus coughed up from the lungs.
• Hoarseness.
• Loss of appetite, or weight loss with no known cause.
• Fatigue, trouble swallowing, or swelling in the face or neck veins.

None of those symptoms points to an ALK fusion specifically. That is settled by testing tumor tissue after a diagnosis, not before one. Our overview of lung cancer covers the types and how they are staged.

The wider picture

The American Cancer Society estimates about 229,410 new lung and bronchus cancers and 124,990 deaths in the United States in 2026, and SEER, NCI's cancer surveillance program, republishes that projection. Lung cancer causes 20% of all US cancer deaths.

Five-year relative survival across all stages was 29.5% for people diagnosed from 2016 through 2022. By stage, 24% are found while local, at 65.5%. Twenty-one percent are found in nearby nodes, at 38.2%. Fifty-one percent are found after distant spread, at 10.5%.

Those figures cover every kind of lung cancer, at every stage, over years. ALK-positive disease is a small slice of it, and these numbers do not describe one person.

What this trial cannot tell you

It cannot tell you anything about lung cancer without an ALK fusion, which is most of it.

It did not establish a survival benefit. Crossover means that question may never be answered cleanly from this trial.

And crizotinib was the first ALK inhibitor, not the last. Newer drugs in the same class have since been compared against it, so a 2014 result describes the state of the field then, not the choice a person faces now.

Sources

• Solomon BJ et al., First-line crizotinib versus chemotherapy in ALK-positive lung cancer, N Engl J Med 2014 (NCBI E-utilities record)
• ClinicalTrials.gov record for NCT01154140 (PROFILE 1014)
• NCI PDQ: Non-Small Cell Lung Cancer Treatment (Patient Version)
• NCI SEER Cancer Stat Facts: Lung and Bronchus 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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