LUX-Lung 3: What the Lung Cancer Trial Found

The screening number tells the story

LUX-Lung 3 screened 1,269 people. It randomized 345.

That ratio is the whole point of the trial. Only patients whose lung adenocarcinoma carried a mutation in the EGFR gene could take part, and most tumors do not. The trial was not asking whether a pill beats chemotherapy in lung cancer. It was asking whether it beats chemotherapy in one genetically defined slice of it.

ClinicalTrials.gov records the study, NCT00949650, as a phase 3 trial that began in August 2009 and reached primary completion in February 2012, with 345 participants.

How it was built

Everyone had stage IIIB or IV lung adenocarcinoma with an EGFR mutation. Participants were grouped first by which mutation they carried, then assigned two to one.

Two thirds received afatinib, 40 mg by mouth once a day. One third received up to six cycles of cisplatin plus pemetrexed, given intravenously every three weeks.

The main measure was progression-free survival, meaning how long people lived before the cancer grew again, judged by independent reviewers rather than the treating doctors. Our page on what standard of care means in a trial explains why the comparison arm matters as much as the new drug.

What EGFR does, and what afatinib does to it

EGFR stands for epidermal growth factor receptor. It sits on the cell surface and tells the cell to divide when the right signal arrives.

Certain mutations jam that switch on. The cell keeps dividing without any outside instruction, and the tumor becomes dependent on that one broken signal.

Afatinib blocks it, and it does so irreversibly, binding rather than simply sitting in the way. It also blocks two related receptors, HER2 and ErbB4.

The results

Median progression-free survival was 11.1 months with afatinib and 6.9 months with chemotherapy. The hazard ratio was 0.58, meaning that at any given moment the risk of the cancer growing or the person dying was about 42% lower on afatinib.

Among the 308 participants with the two most common EGFR mutations, an exon 19 deletion or the L858R change, the gap widened. Median progression-free survival was 13.6 months against 6.9 months, with a hazard ratio of 0.47.

Side effects differed in kind rather than in weight. Afatinib produced diarrhea, an acne-like rash, and mouth sores. Chemotherapy produced nausea, fatigue, and loss of appetite.

Participants also reported better control of cough, breathlessness and pain on afatinib. That result deserves a caveat, which the next section covers.

What it changed

FDA approved afatinib, sold as Gilotrif, on 12 July 2013 under NDA 201292, held by Boehringer Ingelheim.

The wider effect was on practice. LUX-Lung 3 was part of the evidence that made EGFR testing routine before treating advanced lung adenocarcinoma. Before that, a person with a targetable mutation might never have been tested for it.

This is now standard. A tissue sample goes for molecular testing at diagnosis, and the treatment plan waits on the result. Our overview of lung cancer covers where that fits.

Where this trial sits today

Afatinib is no longer the usual first choice. Later EGFR inhibitors have taken that place, and the field has moved on in the decade-plus since.

That is not a criticism of the trial. It is what progress looks like: a result that establishes a principle, then gets overtaken by drugs built on the same principle.

For context on the disease itself, the American Cancer Society projects about 229,410 new lung and bronchus cancer diagnoses in the United States in 2026 and about 124,990 deaths, a projection SEER hosts. SEER's own follow-up puts five-year relative survival at 29.5% across all stages for people diagnosed from 2016 through 2022. That is a population figure and not a statement about any individual.

What this does not mean

• The published primary analysis showed longer progression-free survival, not longer overall survival for the whole randomized group. Those are different questions, and only the first was answered here.
• The trial was open-label. Everyone knew whether they were swallowing a tablet or sitting through an infusion, which can shape self-reported symptom scores. The patient-reported findings should be read with that in mind.
• Afatinib's diarrhea and rash are frequent enough to force dose reductions in ordinary practice. A trial population is generally fitter and more closely monitored than the wider group of people with the same diagnosis.
• The result applies only to people whose tumor carries an EGFR mutation, which is why 924 of the 1,269 people screened were not enrolled.
• Nothing here is a treatment recommendation. Our page on questions to ask about a clinical trial covers what to raise with a team.

Sources

• NCBI eutils: Sequist et al., J Clin Oncol 2013;31:3327-34 (PMID 23816960)
• ClinicalTrials.gov API v2: NCT00949650 (LUX-Lung 3)
• FDA Drugs@FDA overview: GILOTRIF (afatinib), NDA 201292
• NCI SEER 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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