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, Grant D ORCID: 0000-0003-3188-9140, Welsh, Sarah J, Ursprung, Stephan ORCID: 0000-0003-2476-178X, Gallagher, Ferdia A ORCID: 0000-0003-4784-5230, Jones, James O, Shields, Jacqui, Smith, Christopher G ORCID: 0000-0001-7357-2737, Mitchell, Thomas J, Warren, Anne Y, Bex, Axel et al (show 19 more authors) (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.

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Clinical trial registration</h4>NCT03494816.

Item Type: Article
Uncontrolled Keywords: NAXIVA Trial Group, Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Thrombosis, Neoadjuvant Therapy, Nephrectomy, Retrospective Studies, Axitinib
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 07 Jul 2023 15:10
Last Modified: 07 Jul 2023 15:10
DOI: 10.1038/s41416-022-01883-7
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3171542
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