Background
Phase III, double-blind, placebo-controlled RCT (LAURA). N=216 patients with unresectable stage III EGFR-mutated (exon 19 del / L858R) NSCLC without progression after definitive platinum-based chemoradiotherapy. 2:1 randomization.
Interventions and follow up
Arm A: Osimertinib 80 mg PO once daily until progression (N=143)
Arm B: Placebo PO once daily, crossover to osimertinib allowed at progression (N=73)
Primary endpoint: PFS by BICR
mFollow up: 22 mo
Arm B: Placebo PO once daily, crossover to osimertinib allowed at progression (N=73)
Primary endpoint: PFS by BICR
mFollow up: 22 mo
Results
mPFS: 39.1 vs 5.6mo, HR 0.16, 95% CI 0.10–0.24, P<.001
12mo PFS: 74% vs 22%
24mo PFS: 65% vs 13%
OS (immature, 36mo): 84% vs 74%, HR 0.81, 95% CI 0.42–1.56, P=.53
CNS progression: markedly reduced with osimertinib
12mo PFS: 74% vs 22%
24mo PFS: 65% vs 13%
OS (immature, 36mo): 84% vs 74%, HR 0.81, 95% CI 0.42–1.56, P=.53
CNS progression: markedly reduced with osimertinib
Adverse events
Pulmonary: radiation pneumonitis 48% vs 38% (mostly grade 1–2).
GI: diarrhea 36% vs 14%.
Dermatologic: rash 24% vs 14%.
Overall: grade ≥3 AEs 35% vs 12%; safety consistent with known osimertinib profile.
GI: diarrhea 36% vs 14%.
Dermatologic: rash 24% vs 14%.
Overall: grade ≥3 AEs 35% vs 12%; safety consistent with known osimertinib profile.
Conclusions
Osimertinib consolidation after definitive chemoradiotherapy dramatically improved PFS (39.1 vs 5.6mo) in unresectable stage III EGFR-mutated NSCLC. OS data remain immature.
Key Limitations
Baseline brain imaging by PET not required, raising staging concerns. The placebo 12mo PFS (22%) was notably lower than the EGFR subgroup in PACIFIC (~50s%), suggesting possible inclusion of more advanced/under-staged disease that may inflate the apparent magnitude of benefit. OS immature with crossover confounding. Benefit clear but magnitude should be interpreted cautiously in well-staged patients.
Clinical Context
FDA approved osimertinib (Sept 2024) for unresectable stage III EGFR-mutated NSCLC after chemoradiation, establishing it as the new standard in this setting (durvalumab/PACIFIC underperforms in EGFR+ disease). ESMO endorses osimertinib consolidation for EGFR+ stage III after CRT.
References