FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer
Starting with the third-generation EGFR drug osimertinib, rather than saving it for later, kept EGFR-mutated lung cancer under control for almost twice as long and later helped patients live longer.
Double-blind phase 3 trial of 556 patients with untreated advanced non-small-cell lung cancer carrying an EGFR exon 19 deletion or L858R mutation, randomised to osimertinib or a first-generation EGFR inhibitor (gefitinib or erlotinib). Primary endpoint was investigator-assessed PFS.
Median PFS was 18.9 vs 10.2 months (HR 0.46), with fewer central nervous system progressions and less grade 3 toxicity. The 2020 overall survival report showed 38.6 vs 31.8 months (HR 0.80) despite crossover. It made osimertinib the global first-line standard and the backbone on which FLAURA2 and MARIPOSA later built.
- Median PFS 18.9 vs 10.2 months; HR 0.46 (95% CI 0.37-0.57).
- CNS progression events were roughly halved with osimertinib.
- Grade 3 or higher adverse events 34% vs 45%.
- Overall survival (2020): median 38.6 vs 31.8 months, HR 0.80 (95% CI 0.64-1.00), with about 31% of control patients crossing over to osimertinib.
- FLAURA2 (2023) later showed adding platinum-pemetrexed to osimertinib extends PFS further (25.5 vs 16.7 months, HR 0.62).
Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.
- The overall survival benefit was borderline (upper confidence limit 1.00) and diluted by crossover to osimertinib.
- Asian patients and those with L858R had smaller OS gains in subgroup analyses.
- Resistance is universal; the trial did not address what to do after osimertinib.
- High drug cost limits access in many countries where EGFR mutations are common.