Randomized phase III study of adjuvant chemotherapy with or without low-molecular weight heparin in completely resected non-small cell lung cancer patients: The NVALT-8 study.

8506 Background: aCT improves overall survival in pts with completely resected stage II/ III NSCLC. LMWH may also improve survival. We hypothesized that in pts with completely resected NSCLC adding nadroparin (nadro) to aCT will improve recurrence-free survival (RFS). This effect may be different in high/low (SUVmax ≥ 10 vs < 10) FDG avidity NSCLC. Methods: Prospective multicenter phase III study in pts with resectable NSCLC who were randomized within 4-6 wks after surgery to nadro sc daily for 16 wks or no nadro (controle). All pts received 4 cycles pemetrexed (500 mg/m2) for non-squamous or gemcitabine 1000 mg/m2 for squamous histologies and cisplatin (75 mg/m2) on day 1 every 3 wks. Other inclusion criteria: PS 0-2, adequate organ function, INR<1.5. Exclusion criteria: R1 and wedge/segmental resection, prior chemo- or radiotherapy or contra-indication for nadro. Primary endpoint is RFS. Slow accrual enabled to decrease the number of pts from 600 to 202, still providing 80% power to compare RFS at 94 events (α = 0.05; 2-sided log-rank test) in both arms at 3 yrs from 60% to 75%, assuming exponential survival. Cox proportional hazard models were used to evaluate nadro as an independent factor for survival, both in pts with high/low FDG avidity NSCLC. Results: Among235 registered patients, 202 were randomized (nadro: n=100; control n=102), 120 (59%) men, 77 (38%) squamous, 125 (62%) non-squamous, staged pT1N0 (n=1), pT2N0 (n=57), pT1N1 (n=9), pT2N1 (n=51), pT3N0 (n=39) and pT3N1 (n=14), pT4N0 (n=3), 28 had unforeseen mediastinal disease. Among grade ≥ 3 toxicity neutropenia was most common (nadro n=20; control n=6, p= 0.002). No differences in bleeding events occurred. Pts randomized to nadro had a RFS of 47.8 mo vs 36.1 mo in control arm. At 3 yrs, RFS was resp 57 and 50%. Data on OS are immature. When stratified for FDG avidity RFS was different for nadro versus control (HR=0.60, p=0.03). Conclusions: Adjuvant nadroparine improved RFS in high and low FDG avidity NSCLC. Clinical trial information: NTR 1250/1217.