Randomised phase 3 study of adjuvant chemotherapy with or without nadroparin in patients with completely resected non-small-cell lung cancer: the NVALT-8 study

• Published in: British journal of cancer 2019-08, Vol.121 (5), p.372-377
• Main Authors: Groen, Harry J. M., van der Heijden, Erik H. F. M., Klinkenberg, Theo J., Biesma, Bonne, Aerts, Joachim, Verhagen, Ad, Kloosterziel, Corinne, Pieterman, Remge, van den Borne, Ben, Smit, Hans J. M., Hoekstra, Otto, Schramel, Frans M. N. H., van der Noort, Vincent, van Tinteren, Harm, Smit, Egbert F., Dingemans, Anne-Marie C.
• Format: Article
• Language: English
• Subjects: 631/67/1612/1350; 692/4028/67/1612/1350; Aged; Anticoagulants - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Chemotherapy; Chemotherapy, Adjuvant; Cisplatin - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Disease-Free Survival; Drug Resistance; Epidemiology; Female; Fluorodeoxyglucose F18; Heparin; Humans; Low molecular weights; Lung cancer; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Metastases; Middle Aged; Molecular Medicine; Molecular weight; Nadroparin - therapeutic use; Neoplasm Recurrence, Local - epidemiology; Neoplasm Staging; Non-small cell lung carcinoma; Oncology; Patients; Pemetrexed - administration & dosage; Pneumonectomy; Positron-Emission Tomography; Randomization; Surgery
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-019-0533-3

Background Retrospective studies suggest that low molecular weight heparin may delay the development of metastasis in patients with resected NSCLC. Methods Multicentre phase 3 study with patients with completely resected NSCLC who were randomised after surgery to receive chemotherapy with or without nadroparin. The main exclusion criteria were R1/2 and wedge/segmental resection. FDG-PET was required. The primary endpoint was recurrence-free survival (RFS). Results Among 235 registered patients, 202 were randomised (nadroparin: n  = 100; control n  = 102). Slow accrual enabled a decrease in the number of patients needed from 600 to 202, providing 80% power to compare RFS with 94 events (α = 0.05; 2-sided). There were no differences in bleeding events between the two groups. The median RFS was 65.2 months (95% CI, 36—NA) in the nadroparin arm and 37.7 months (95% CI, 22.7—NA) in the control arm (HR 0.77 (95% CI, 0.53–1.13, P  = 0.19). FDG-PET SUVmax ≥10 predicted a greater likelihood of recurrence in the first year (HR 0.48, 95% CI 0.22–0.9, P  = 0.05). Conclusions Adjuvant nadroparin did not improve RFS in patients with resected NSCLC. In this study, a high SUVmax predicted a greater likelihood of recurrence in the first year. Clinical trial registration Netherlands Trial registry: NTR1250/1217.