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)
Grant D. Stewart, Sarah J. Welsh, Stephan Ursprung, Ferdia A. Gallagher, James O. Jones, Jacqui Shields, Christopher G. Smith, Thomas J. Mitchell, Anne Y. Warren, Axel Bex, Ekaterini Boleti, Jade Carruthers, Tim Eisen, Kate Fife, Abdel Hamid, Alexander Laird, Steve Leung, Jahangeer Malik, Iosif Mendichovszky, Faiz Mumtaz, Grenville Oades, Andrew N. Priest, Antony C. P. Riddick, Balaji Venugopal, Michelle Welsh, Kathleen Riddle, Lisa Hopcroft, NAXIVA Trial Group, Niki Couper, Lisa Hopcroft, Robert Hill, Athena Matakidou, Cara Caasi, James Watson, Lauren Wallis, Ruby Cross, Sarah Burge, Anne George, Tobias Klatte, Tevita Aho, James N. Armitage, Sabrina Rossi, Charles Massie, Shubha Anand, Tiffany Eira Haddow, Marc Dodd, Wenhan Deng, Jose‐Ezequiel Martín, Philip Howden, Stephanie Wenlock, Evis Sala, Stefan N. Symeonides, Lynn Ho, Jennifer Baxter, Stuart W. Leslie, Duncan McLaren, John E. Brush, Marie O’Donnell, Alisa Griffin, Ruth Orr, Catriona Cowan, Thomas Powles, Anna Pejnovic, Sophia Tincey, Lee Alexander Grant, Martin Nuttall, Lucy Willsher, Christian Barnett, David Nicol, James Larkin, Alison Fielding, Robert J. Jones
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. CLINICAL TRIAL REGISTRATION: NCT03494816.