A phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA)

Stewart, G. D. et al. (2022) A phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA). British Journal of Cancer, 127(6), pp. 1051-1060. (doi: 10.1038/s41416-022-01883-7) (PMID:35739300) (PMCID:PMC9470559)

Abstract

Background: Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. Methods: NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. Results: In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. Conclusions: NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery.

• Item Type: Articles
• Additional Information: NAXIVA was endorsed by Cancer Research UK (A23471). We acknowledge the support of the National Institute for Health Research Clinical Research Network (NIHR CRN). Funding and Medicine for this Investigator Sponsored Research study was provided by Pfizer Ltd. GDS and AYW are supported by The Mark Foundation for Cancer Research, the Cancer Research UK Cambridge Centre [C9685/A25177] and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The Cambridge Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hopcroft, Dr Lisa and Venugopal, Dr Balaji and Jones, Professor Robert
• Authors: Stewart, G. D., Welsh, S. J., Ursprung, S., Gallagher, F. A., Jones, J. O., Shields, J., Smith, C. G., Mitchell, T. J., Warren, A. Y., Bex, A., Boleti, E., Carruthers, J., Eisen, T., Fife, K., Hamid, A., Laird, A., Leung, S., Malik, J., Mendichovszky, I. A., Mumtaz, F., Oades, G., Priest, A. N., Riddick, A. C.P., Venugopal, B., Welsh, M., Riddle, K., Hopcroft, L. E.M., NAXIVA Trial Group, , and Jones, R. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: British Journal of Cancer
• Publisher: Springer Nature
• ISSN: 0007-0920
• ISSN (Online): 1532-1827
• Published Online: 23 June 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in British Journal of Cancer 127(6): 1051-1060
• Publisher Policy: Reproduced under a Creative Commons License