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Clinical Trial
. 2019 Aug;121(5):372-377.
doi: 10.1038/s41416-019-0533-3. Epub 2019 Jul 24.

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

Harry J M Groen  1 , Erik H F M van der Heijden  2 , Theo J Klinkenberg  3 , Bonne Biesma  4 , Joachim Aerts  5 , Ad Verhagen  6 , Corinne Kloosterziel  7 , Remge Pieterman  8 , Ben van den Borne  9 , Hans J M Smit  10 , Otto Hoekstra  11 , Frans M N H Schramel  12 , Vincent van der Noort  13 , Harm van Tinteren  13 , Egbert F Smit  14 , Anne-Marie C Dingemans  15 ; NVALT Study Group, the Netherlands
Affiliations
Clinical Trial

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

Harry J M Groen et al. Br J Cancer. 2019 Aug.

Abstract

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.

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Conflict of interest statement

H.J.M.G., E.F.S. and A.-M.D. were on the advisory boards of Lilly and Roche. The remaining authors authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Consort diagram for the NVALT-8 study of patients registered in 15 hospitals between December 2007 and July 2013
Fig. 2
Fig. 2
Recurrence-free survival in patients with resected NSCLC treated with adjuvant chemotherapy with or without nadroparin. CP/CG +N is cisplatin and pemetrexed/cisplatin and gemcitabine + nadroparin. HR was 0.77 (95% CI., 0.53–1.13, P = 0.19)
Fig. 3
Fig. 3
a/b Recurrence-free survival in patients with resected NSCLC treated with adjuvant chemotherapy with or without nadroparin stratified into SUVmax-based risk groups. High risk is defined as SUVmax ≥10 in the primary tumour, while the low risk is defined as SUVmax <10. For FDG-based risk groups, the HR was 0.70 (95% CI., 0.46–1.04, P = 0.08)
Fig. 4
Fig. 4
Overall survival in patients with resected NSCLC stratified by treatment arm. CP/CG +N is cisplatin and pemetrexed/cisplatin and gemcitabine + nadroparin. The HR was 0.70 (95% CI 0.46–1.08, P = 0.10)
See this image and copyright information in PMC

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