FDA Approval: Erlotinib (Tarceva) for Lung Cancer

The decision

The FDA approved Tarceva (erlotinib) tablets on November 18, 2004.

The approval letter describes the use precisely. Tarceva was cleared for locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. It was a second-line drug from day one.

This was not an accelerated approval. It rested on a randomized trial with survival as the primary endpoint.

What EGFR is, and why a pill can block it

EGFR stands for epidermal growth factor receptor. It is a protein that sits on the surface of many cells and tells them to grow when it receives a signal.

Some lung cancers carry changes in the EGFR gene that leave this switch stuck on. Erlotinib blocks the receptor's activity from inside the cell. That is what makes it a targeted therapy rather than chemotherapy, which attacks dividing cells generally.

Testing tumor tissue for changes like this is now routine, and our page on biomarker testing explains what those tests look for.

The trial

The evidence was a randomized, double-blind, placebo-controlled trial in 731 people with locally advanced or metastatic non-small cell lung cancer whose disease had already progressed after chemotherapy.

They were assigned two to one: 488 received Tarceva 150 mg once a day by mouth, and 243 received placebo. The primary endpoint was overall survival.

Median survival was 6.7 months on Tarceva against 4.7 months on placebo. The hazard ratio was 0.73, with a 95% confidence interval of 0.61 to 0.86 and a p-value below 0.001.

Survival at one year was 31.2% against 21.5%. Median progression-free survival, the time before the cancer grew again, was 9.9 weeks against 7.9 weeks, with a hazard ratio of 0.59.

Tumors shrank in 8.9% of the Tarceva group against 0.9% on placebo, and those responses lasted a median of 34.3 weeks against 15.9 weeks.

Reading two months honestly

A two-month difference in median survival is a real effect and a small one. Both facts belong in the same sentence.

For people out of chemotherapy options in 2004, a daily pill that moved that number at all was significant. It is not a description of what any single person gained, because a median is the midpoint of a spread: some people in that trial gained far more time, and some gained none.

The label also reported a subgroup finding. Among the 127 people whose tumors tested EGFR positive, the survival hazard ratio was 0.65. But the label is careful to say a benefit in the EGFR negative subgroup, at 111 people, cannot be excluded, because the confidence intervals for the subgroups are wide and overlapping. EGFR status was known for only 238 of the 731 patients — a third — since it could only be measured where tissue already existed before enrollment.

What taking it involves

The dose was one 150 mg tablet a day.

The most common side effects were rash and diarrhea. Severe rash or diarrhea, graded 3 or 4, occurred in 9% and 6% of people on the drug. Rash appeared at a median of 8 days and diarrhea at a median of 12 days, so both tend to show up in the first two weeks.

The label also carried a warning about interstitial lung disease, an inflammation and scarring of lung tissue that was reported infrequently but can be serious.

When to get checked

Lung cancer often causes nothing early and is sometimes found on a chest x-ray ordered for something else. NCI lists these as reasons to see a doctor:

• 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.

There is also screening for people at high risk, using low-dose CT. NCI's clinical summary describes the National Lung Screening Trial, which enrolled 53,454 people aged 55 to 74 with at least a 30 pack-year smoking history, including former smokers who had quit within the past 15 years. Three annual low-dose CT scans cut lung cancer deaths by 20% compared with chest x-rays.

That trial also shows the cost of screening: 39.1% of the CT group had at least one positive result, and only 3.6% of those positives turned out to be cancer.

The survival picture

SEER, NCI's cancer surveillance program, lists about 229,410 new lung and bronchus cancers and 124,990 deaths in the United States for 2026, a projection the American Cancer Society produces. Lung cancer accounts for 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, SEER records 24% 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 are population averages from past years and do not describe any individual.

What this approval cannot tell you

The 2004 trial enrolled people regardless of EGFR status, because routine testing did not yet exist. Its results describe a mixed population, not the biomarker-selected group who would be offered an EGFR drug today.

The approval also did not make erlotinib a first treatment. Its 2004 indication began only after chemotherapy had failed.

And a two-month median gain in a trial says nothing about what one person will experience. That question belongs to a specific tumor, a specific test result, and a specific care team.

Sources

• FDA approval letter for Tarceva (erlotinib) tablets, NDA 21-743
• FDA 2004 prescribing information for Tarceva (erlotinib)
• Drugs@FDA overview: TARCEVA, NDA 021743
• NCI PDQ: Non-Small Cell Lung Cancer Treatment (Patient Version)
• NCI PDQ: Lung Cancer Screening (Health Professional Version)
• NCI SEER Cancer Stat Facts: Lung and Bronchus Cancer
• American Cancer Society: Cancer Facts & Statistics

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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