Background
Phase 3, open-label, randomised controlled trial (60 hospitals, China). N=624 treatment-naive, locally advanced or metastatic NSCLC with EGFR-sensitizing mutations (ex19del or L858R); ECOG 0–1; neurologically stable brain metastases permitted. Tests whether adding platinum–pemetrexed chemotherapy to the third-generation EGFR-TKI aumolertinib improves first-line outcomes.
Results
Interventions and follow up: Arm A: Aumolertinib 110mg PO once daily + pemetrexed 500mg/m² + cisplatin 75mg/m² or carboplatin AUC5 IV q3wk ×4–6, then maintenance aumolertinib + pemetrexed (n=310)
Arm B: Aumolertinib 110mg PO once daily monotherapy (n=314)
Primary endpoint: PFS by blinded independent central review (RECIST 1.1)
mFollow up: 23.4 months
Results: PFS (BICR): 28.9 vs 18.9mo, HR 0.47, 95% CI 0.37–0.60, P<.0001
PFS (investigator): 28.4 vs 19.7mo
OS: NR (immature at data cutoff)
Arm B: Aumolertinib 110mg PO once daily monotherapy (n=314)
Primary endpoint: PFS by blinded independent central review (RECIST 1.1)
mFollow up: 23.4 months
Results: PFS (BICR): 28.9 vs 18.9mo, HR 0.47, 95% CI 0.37–0.60, P<.0001
PFS (investigator): 28.4 vs 19.7mo
OS: NR (immature at data cutoff)
Adverse events
Grade 3–4 (any): 79.6% (combination) vs 34.8% (monotherapy)
Hematologic (G3–4, combo vs mono): neutropenia 55% vs 1%, WBC decreased 34% vs <1%, thrombocytopenia 20% vs 1%
Serious AEs: 36% vs 17%
Treatment-related deaths: 1 (<1%, encephalopathy) vs 2 (1%)
Hematologic (G3–4, combo vs mono): neutropenia 55% vs 1%, WBC decreased 34% vs <1%, thrombocytopenia 20% vs 1%
Serious AEs: 36% vs 17%
Treatment-related deaths: 1 (<1%, encephalopathy) vs 2 (1%)
Conclusions
Adding platinum–pemetrexed to first-line aumolertinib extended median PFS by ~10 months (28.9 vs 18.9mo; HR 0.47) in EGFR-mutant advanced NSCLC, at the cost of substantially more hematologic toxicity. OS remains immature. Supports TKI-plus-chemotherapy intensification as a first-line option, echoing FLAURA2.
Key Limitations
Open-label design; conducted entirely in China, leaving generalizability to other populations uncertain; OS immature; the combination markedly increases hematologic toxicity (G3–4 neutropenia 55%); the control arm is aumolertinib monotherapy rather than osimertinib, and aumolertinib is not approved outside China; no ctDNA/MRD-defined subgroup to identify which patients actually need added chemotherapy.
Clinical Context
Validates the FLAURA2 paradigm (third-generation EGFR-TKI + platinum–pemetrexed) in first-line EGFR-mutant advanced NSCLC. Aumolertinib (Ameile; Hansoh) is approved in China but not by the FDA or EMA, so this regimen is most relevant where aumolertinib is available. NCCN, ASCO and ESMO already list osimertinib ± chemotherapy among preferred first-line options; AENEAS2 adds regional evidence for TKI–chemo intensification. OS data are awaited before firm positioning.