ANITA

Background

Phase III, open-label RCT (ANITA). N=840 patients with completely resected stage IB–IIIA NSCLC (1997 UICC staging), ECOG PS 0–2, age ≤75. No prior adjuvant chemotherapy. Benchmark cytotoxic adjuvant trial establishing platinum-doublet benefit.

Interventions and follow up

Arm A: Vinorelbine 30 mg/m² IV days 1 and 8 + cisplatin 100 mg/m² IV day 1 q3wk × 4 cycles (N=407)
Arm B: Observation (N=433)
Primary endpoint: Overall survival
mFollow up: 76 mo

Results

OS: HR 0.80, 95% CI 0.66–0.96, P=.017
mOS: 65.7 vs 43.7 months
5-yr OS (stages II–IIIA): 51.2% vs 42.6%
DFS: HR 0.76, 95% CI 0.64–0.90, P=.001
Stage IB: no significant OS benefit

Adverse events

Hematologic: grade 3–4 neutropenia 85%; febrile neutropenia 7.9%.
GI: grade ≥3 nausea/vomiting 21%.
Overall: treatment-related deaths 2 (0.5%).

Conclusions

Adjuvant vinorelbine + cisplatin significantly improved OS in resected NSCLC (HR 0.80), establishing platinum-based doublet chemotherapy as standard adjuvant treatment for stage II–IIIA NSCLC. No benefit was demonstrated in stage IB.

Key Limitations

High-dose cisplatin (100 mg/m²) exceeds currently used doses (75 mg/m²) with higher hematologic toxicity. No benefit in stage IB. Used 1997 staging — stage categories differ from contemporary 8th edition UICC, complicating cross-trial comparison. No biomarker selection. Now largely superseded in EGFR/ALK-mutated patients by targeted adjuvant agents.

Clinical Context

ANITA, with IALT and the LACE meta-analysis, established adjuvant platinum-doublet chemotherapy as standard for stage II–IIIA resected NSCLC (~5% absolute OS benefit at 5 years). This standard is now refined by EGFR TKIs (ADAURA), ALK inhibitors (ALINA), and IO (IMpower010, KEYNOTE-091) in biomarker-selected populations. ESMO-MCBS score: 3.

References

Douillard JY et al, Lancet 2006 (primary OS) | Pignon JP et al, J Natl Cancer Inst 2006 (LACE meta-analysis)