Background
Phase III, double-blind RCT; N=682; resected stage IB-IIIA EGFR-mutated (ex19del/L858R) NSCLC; randomized 1:1; adjuvant chemotherapy permitted before randomization.
Interventions and follow up
Arm A: Osimertinib 80 mg PO daily up to 3 yr
Arm B: Placebo
Primary endpoint: DFS in stage II-IIIA
Secondary endpoints: DFS overall population, OS, safety
mFollow up: 22 mo (primary); ~5 yr (OS update)
Arm B: Placebo
Primary endpoint: DFS in stage II-IIIA
Secondary endpoints: DFS overall population, OS, safety
mFollow up: 22 mo (primary); ~5 yr (OS update)
Results
DFS (stage II-IIIA): NR vs 19.6 mo; HR 0.17 (95%CI 0.11–0.26); P<.001
DFS (overall population): NR vs 27.5 mo; HR 0.20 (95%CI 0.14–0.30); P<.001
5-yr OS update (Tsuboi 2023, PMID 37272535):
5-yr OS (stage II-IIIA): 85% vs 73%; HR 0.49 (95.03%CI 0.33–0.73); P<.001
OS by stage IB: HR 0.44 (95%CI 0.17–1.02)
OS by stage II: HR 0.63 (95%CI 0.34–1.12)
OS by stage IIIA: HR 0.37 (95%CI 0.20–0.64)
OS, received adjuvant chemo: HR 0.49 (95%CI 0.30–0.79)
OS, no adjuvant chemo: HR 0.47 (95%CI 0.25–0.83)
DFS (overall population): NR vs 27.5 mo; HR 0.20 (95%CI 0.14–0.30); P<.001
5-yr OS update (Tsuboi 2023, PMID 37272535):
5-yr OS (stage II-IIIA): 85% vs 73%; HR 0.49 (95.03%CI 0.33–0.73); P<.001
OS by stage IB: HR 0.44 (95%CI 0.17–1.02)
OS by stage II: HR 0.63 (95%CI 0.34–1.12)
OS by stage IIIA: HR 0.37 (95%CI 0.20–0.64)
OS, received adjuvant chemo: HR 0.49 (95%CI 0.30–0.79)
OS, no adjuvant chemo: HR 0.47 (95%CI 0.25–0.83)
Adverse events
Constitutional: any-grade AEs 98% vs 89%
GI: diarrhea 46%; stomatitis grade 3-4 2%
Skin/nail: paronychia 25%
Pulmonary: interstitial lung disease 3% (osimertinib)
Grade 3-4 overall: 20% vs 13% (diarrhea 2%)
GI: diarrhea 46%; stomatitis grade 3-4 2%
Skin/nail: paronychia 25%
Pulmonary: interstitial lung disease 3% (osimertinib)
Grade 3-4 overall: 20% vs 13% (diarrhea 2%)
Conclusions
Adjuvant osimertinib for resected stage IB-IIIA EGFR-mutated NSCLC significantly improved DFS and, at the 5-yr update, OS.
Key Limitations
Optimal duration (3 yr fixed) and post-recurrence efficacy of osimertinib rechallenge undefined; many recurrences occurred after treatment completion; CNS DFS benefit but limited OS data by subgroup; adjuvant chemo not mandated.
Clinical Context
FDA approved Dec 2020 (resected stage IB-IIIA EGFR ex19del/L858R NSCLC) and 2024 expanded to include adjuvant after the LAURA/OS data; ESMO/ASCO endorse 3 yr adjuvant osimertinib. Standard adjuvant option after complete resection and platinum chemo; LAURA addresses the unresectable stage III setting.