ANITA: Phase III adjuvant vinorelbine (N) and cisplatin (P) versus observation (OBS) in completely resected (stage I-III) non-small-cell lung cancer (NSCLC) patients (pts): Final results after 70-month median follow-up. On behalf of the Adjuvant Navelbine International Trialist Association
7013 Background: Adjuvant chemotherapy demonstrated a 5–15% benefit in 5-year survival in the IALT, JBR10 and CALGB9633 trials. However, other trials were negative (ALPI, ECOG 3590) and the role of chemotherapy for each disease stage has not yet been completely clarified. The randomized, prospective phase III trial ANITA compared the effectiveness of adjuvant NP versus OBS in early NSCLC. Methods: Completely resected pts were randomized to receive adjuvant NP (N 30 mg/m2/week, 16 administrations plus P 100 mg/m2 d1 q4 weeks for 4 cycles) or OBS. Eligibility criteria included histologically proven NSCLC, age 18–75 years, post-operative stage I (T2N0), II or IIIA. Radiotherapy policy was predetermined by each center. Study design: open, multicenter, randomized (1:1), stratified by center, stage and histology. Main endpoint: overall survival. Assuming 5% alfa error and 90% power to demonstrate a 10% improvement in survival at 2 years, 400 patients per arm had to be included. Results: 840 patients (NP 407; OBS 433) from 101 centers in 14 countries were included between 12/94 and 12/00. Median age: 59 (range 18–75); 86% male; 95% WHO PS 0–1; 59% squamous cell carcinoma; 35% stage I, 30% II, 35% IIIA. Pneumonectomy was performed in 37% of pts and lobectomy in 58%. Arms were well-balanced with regard to age, gender, histology, staging and resection type. Median follow-up is currently >70 months. Median survival was 65.8 months in NP and 43.7 months in OBS (P=0.0131; hazard ratio, 1.264 [1.05–1.52]). Survival at 2/5/7 years was 68%/51%/45% in NP and 63%/43%/37% in OBS. 5-year survival by stage I/II/IIIA were 62%/52%/42% in NP and 63%/39%/26% in OBS. Grade 3/4 toxicities in NP were manageable: neutropenia 86%; febrile neutropenia 8.5%; nausea-vomiting 27%; constipation 5%; peripheral neuropathy 3%. 5 pts (1%) died of drug-related toxicity. Conclusion: The ANITA results demonstrate that NP significantly improves survival in completely resected stage II and IIIA NSCLC pts, although no benefit was observed in stage I. No significant financial relationships to disclose.