Background
Phase III, open-label, randomized controlled trial (ADJUVANT/CTONG1104). N=222 patients with completely resected stage II–IIIA NSCLC with EGFR activating mutations (exon 19 del or L858R) confirmed by ARMS PCR, R0 resection. First prospective RCT of EGFR TKI in adjuvant NSCLC. Chinese multicenter study.
Interventions and follow up
Arm A: Gefitinib 250 mg PO daily × 24 months (N=111)
Arm B: Cisplatin 75 mg/m² IV day 1 + vinorelbine 25 mg/m² IV days 1 and 8 q3wk × 4 cycles (N=111)
Primary endpoint: Disease-free survival
mFollow up: 80 months (OS update 2021)
Arm B: Cisplatin 75 mg/m² IV day 1 + vinorelbine 25 mg/m² IV days 1 and 8 q3wk × 4 cycles (N=111)
Primary endpoint: Disease-free survival
mFollow up: 80 months (OS update 2021)
Results
mDFS: 28.7 vs 18.0 mo (gefitinib vs chemo), HR 0.60, 95% CI 0.42-0.87, P=.005
OS: no significant difference, HR 0.92, 95% CI 0.60-1.42, P=.693
OS updated 2021: mOS 75.5 vs 70.6 mo — no OS benefit
OS: no significant difference, HR 0.92, 95% CI 0.60-1.42, P=.693
OS updated 2021: mOS 75.5 vs 70.6 mo — no OS benefit
Adverse events
Overall Grade ≥3: 12.3% (gefitinib) vs 48.3% (chemo)
Gefitinib-related Grade ≥3: elevated ALT 4.5%, rash 2.7%
Chemotherapy Grade ≥3: neutropenia 67.3%; plus expected nausea, vomiting, myelosuppression
Other: no new gefitinib safety signals
Gefitinib-related Grade ≥3: elevated ALT 4.5%, rash 2.7%
Chemotherapy Grade ≥3: neutropenia 67.3%; plus expected nausea, vomiting, myelosuppression
Other: no new gefitinib safety signals
Conclusions
Gefitinib significantly improved DFS vs platinum-doublet chemotherapy in EGFR-mutated stage II–IIIA NSCLC (HR 0.60), with markedly better tolerability. No OS benefit was demonstrated, likely due to crossover at recurrence. Landmark proof-of-concept trial for EGFR TKI adjuvant therapy.
Key Limitations
DFS advantage not translated into OS benefit — possibly due to post-recurrence salvage EGFR TKIs or chemotherapy obscuring the signal. Gefitinib (1st-gen TKI) provides no T790M resistance coverage. 2-year duration may be insufficient. Single-ethnicity (Chinese) design limits generalizability. ADAURA (osimertinib, 3rd-gen) subsequently demonstrated OS benefit, rendering gefitinib adjuvant largely obsolete where osimertinib is available.
Clinical Context
ADJUVANT/CTONG1104 established the DFS proof-of-concept for EGFR TKI adjuvant therapy, followed by EVAN (erlotinib), IMPACT (gefitinib Japan — negative), and ADAURA (osimertinib, OS benefit). Per ASCO and ESMO, gefitinib adjuvant is no longer recommended where osimertinib is available. Historical landmark only. ESMO-MCBS: 2 (no OS benefit).