FLAURA: What the Lung Cancer Trial Found

The question was which EGFR pill to go first

By 2014, lung cancer with an EGFR mutation was already treated with a targeted pill rather than chemotherapy. Gefitinib and erlotinib were the usual choices.

Osimertinib was designed for a later problem. When those first-generation pills stop working, it is often because the cancer has acquired a second change called T790M, and osimertinib blocks that as well. FLAURA asked whether the newer drug should be used from the start instead of being held in reserve.

Who was enrolled

Field	Detail
Trial	FLAURA
Identifier	NCT02296125
Phase	Phase 3
Design	Randomised, double-blind
Cancer type	Untreated advanced non-small-cell lung cancer with an EGFR mutation
Comparator	Osimertinib 80 mg daily against gefitinib 250 mg or erlotinib 150 mg daily
Primary endpoint	Progression-free survival, assessed by the investigator

These are the amounts the trial compared. Your own prescription governs what you swallow, and it can be lowered for side effects.

556 people were randomised, half to each side. All had advanced disease not yet treated, and all carried one of the two common EGFR mutations: an exon 19 deletion or L858R. Neither patients nor doctors knew which pill was which.

Note the primary endpoint. It was time before the cancer grew. Survival was a secondary measure, and had to wait.

Nearly nine extra months before the cancer grew

Median progression-free survival was 18.9 months with osimertinib and 10.2 months with the older pills. The hazard ratio was 0.46 (95% CI 0.37 to 0.57, p<0.001).

At an interim look, 83% of the osimertinib group and 71% of the comparator group were alive at 18 months (hazard ratio 0.63, 95% CI 0.45 to 0.88, p=0.007) — a p-value that did not count as significant at that stage of the trial.

Why the response rate is the wrong thing to look at

Tumours shrank in 80% of the osimertinib group and 76% of the comparator group. That difference was not significant (odds ratio 1.27, 95% CI 0.85 to 1.90, p=0.24).

Both drugs, in other words, worked at first for roughly the same share of people. What separated them was how long it lasted: a median response duration of 17.2 months (95% CI 13.8 to 22.0) against 8.5 months (95% CI 7.3 to 9.8). Osimertinib did not start better. It held longer.

Severe side effects, grade 3 or higher, were less common with osimertinib: 34% against 45%.

The survival number came later, and only just

The final survival analysis was published in 2020. Median overall survival was 38.6 months (95% CI 34.5 to 41.8) with osimertinib and 31.8 months (95% CI 26.6 to 36.0) with the comparator. The hazard ratio for death was 0.80, with a 95.05% confidence interval of 0.64 to 1.00 and a p-value of 0.046.

That interval touches 1.00. The result cleared the line by a very small margin, on a secondary endpoint. It is supportive evidence, not the trial's main claim.

By three years, 28% of the osimertinib group were still on their assigned drug, against 9% of the comparator group. Grade 3 or higher side effects at that point were 42% against 47%, despite far longer exposure on osimertinib.

What this trial cannot tell you

• How osimertinib compares with today's alternatives. The comparator was gefitinib or erlotinib alone. Combinations of an EGFR drug with chemotherapy, and other newer approaches, were not in this trial.
• What to expect with an uncommon EGFR mutation. Only exon 19 deletions and L858R were eligible.
• Whether the survival gain is solid. A p-value of 0.046 on a secondary endpoint should be read with care.
• What to do when it stops working. FLAURA tested first treatment, not what comes after.

Questions about EGFR-mutated lung cancer

• Which EGFR mutation do I have, and was it one of the two studied here?
• Is the plan a pill alone, or a pill with something added?
• When this stops working, will you biopsy again to see why?

Sources

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

• NEJM: Osimertinib in Untreated EGFR-Mutated Advanced NSCLC (FLAURA) (primary)
• NEJM: Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC (FLAURA) (primary)

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

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