FLAURA trial

Background

Phase III, double-blind RCT; N=556; previously untreated EGFR-mutation-positive (ex19del or L858R) advanced NSCLC; randomized to osimertinib vs standard EGFR-TKI.

Interventions and follow up

Arm A: Osimertinib 80 mg PO daily
Arm B: Erlotinib 150 mg or gefitinib 250 mg PO daily
Primary endpoint: PFS
Secondary endpoints: OS, ORR, DoR, disease control rate
mFollow up: 15 mo (PFS); ~35 mo (OS update)

Results

mPFS: 18.9 mo vs 10.2 mo; HR 0.46 (95%CI 0.37–0.57); P<.001
ORR: 80% vs 76%; OR 1.27 (95%CI 0.85–1.90); P=.24
mOS (final, Ramalingam 2020): 38.6 mo vs 31.8 mo; HR 0.80 (95.05%CI 0.64–1.00); P=.046
1-yr OS: 89% vs 83%
2-yr OS: 74% vs 59%
3-yr OS: 54% vs 44%

Adverse events

Skin: rash 58% vs 78%; dry skin 36% vs 36%
GI: diarrhea 58% vs 57%
Cardiac: prolonged QT 10% vs 5%
Pulmonary: ILD 4% vs 2%
Grade 3-4 overall: 34% vs 45% (mainly diarrhea, decreased appetite)
Discontinuation for AEs: 13% vs 18%

Conclusions

First-line osimertinib was superior to first-generation TKIs (erlotinib/gefitinib) in PFS and OS for advanced EGFR-mutated NSCLC, establishing it as a preferred first-line option.

Key Limitations

Comparator was first-generation TKI (not later-generation or combination); CNS benefit shown but limited by design; resistance mechanisms (e.g., MET, C797S) and optimal subsequent therapy not addressed; modest OS gain.

Clinical Context

FDA approved first-line osimertinib Apr 2018; ESMO and ASCO list osimertinib as a preferred first-line option for EGFR ex19del/L858R advanced NSCLC. Later trials (FLAURA2 chemo combo, MARIPOSA amivantamab+lazertinib) build on this backbone.

References