Background
Phase III RCT (NEJ009); N=345 chemo-naïve EGFR-mutated advanced NSCLC; gefitinib alone vs gefitinib + carboplatin/pemetrexed; open-label, Japanese.
Interventions and follow up
Arm A: Gefitinib 250 mg PO daily + carboplatin AUC5 + pemetrexed 500 mg/m² IV q3w ×6, then gefitinib + pemetrexed maintenance
Arm B: Gefitinib 250 mg PO daily
Primary endpoint: PFS, PFS2, and OS
mFollow up: NR
Arm B: Gefitinib 250 mg PO daily
Primary endpoint: PFS, PFS2, and OS
mFollow up: NR
Results
mPFS: 20.9 vs 11.9mo, HR 0.49, 95% CI 0.39–0.63, P<.001
mOS: 50.9 vs 38.8mo, HR 0.722, 95% CI 0.55–0.95, P=.021
ORR: 84.0% vs 67.4%, P<.001
mOS: 50.9 vs 38.8mo, HR 0.722, 95% CI 0.55–0.95, P=.021
ORR: 84.0% vs 67.4%, P<.001
Adverse events
Overall: Grade ≥3 TRAEs 65.3% vs 31.0% (combination higher); one fatal infection in Arm A.
Hematologic: neutropenia 31.2% vs 0.6%; anemia 21.2% vs 17.1%; thrombocytopenia 17.1% vs 0%.
Hepatic: elevated LFTs 12.4% vs 22.2% (more common with gefitinib alone).
Hematologic: neutropenia 31.2% vs 0.6%; anemia 21.2% vs 17.1%; thrombocytopenia 17.1% vs 0%.
Hepatic: elevated LFTs 12.4% vs 22.2% (more common with gefitinib alone).
Conclusions
Adding carboplatin/pemetrexed to gefitinib significantly improved PFS and OS in EGFR-mutated advanced NSCLC. A treatment option balanced against increased toxicity.
Key Limitations
Open-label; Japanese-only population (generalizability); gefitinib comparator, not osimertinib (now 1L standard); OS not multiplicity-controlled.
Clinical Context
Proof of concept for TKI + chemo intensification; concept later confirmed with osimertinib in FLAURA2. ESMO recognizes TKI + platinum chemo as a 1L option in EGFR-mutant NSCLC.