Clinical Study

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

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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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Acknowledgements

We thank the NVALT data managers for all their work and the patients who participated in the trial.

Author contributions

H.J.M.G., E.F.S. and A.-M.D. designed the study and wrote the manuscript. V.vd.N., H.v.T. and H.J.M.G. analysed and interpreted the data. All authors contributed to discussions about the design of the study, enrolled the patients, and read and approved the manuscript.

Author information

Correspondence to Harry J. M. Groen.

Ethics declarations

Competing interests

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.

Ethics approval and consent to participate

The study was approved by the medical ethics committee of the University Medical Center Groningen in the Netherlands (METc nr. 2007-076). All patients gave informed consent. The study was registered at NTR 1250 (new ID 1205). The study was performed in accordance with the Declaration of Helsinki.

Funding

This work was financially supported with regard to the drug supply and data management by Eli Lilly, Amgen, Roche, and the Dutch Cancer Society.

Consent to publish

The study should be published according to our protocol that was approved by the medical ethics committee.

Data availability

The dataset used and analysed in the current study is available from the corresponding author on reasonable request. All data are stored at the NVALT Data Center at the National Cancer Center Netherlands.

Note

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

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