CRUK Cambridge Centre Urological Malignancies programme co-lead and Mark Foundation for Integrated Cancer Medicine co-lead Professor Grant Stewart presented the findings of our NAXIVA study in an oral abstract session at ASCO GU 2021. NAXIVA is a phase II feasibility study investigating the effectiveness of the drug axitinib at reducing the extent of cancer invasion into the large blood vessels draining the kidney, which can sometimes extend to the heart.
Professor Stewart, who is Professor of Surgical Oncology at the University of Cambridge, outlined the high morbidity and mortality risk to clear cell renal cell carcinoma (ccRCC; the commonest form of kidney cancer) patients undergoing venous tumour thrombus (VTT) surgery. With VTT surgery mortality rates from 5-15%, downsizing the thrombus with a pre-surgical, neoadjuvant targeted therapy is appealing.
To be eligible for NAXIVA, patients with localised or metastatic kidney cancer with a tumour thrombus underwent an MRI to evaluate the level of the thrombus and a biopsy to confirm ccRCC. Prior to surgery, patients took axitinib for eight weeks, had a safety MRI at three weeks, a further MRI before surgery, then surgery with tumour thrombectomy.
The primary endpoint was a reduction in the level of the tumour thrombus between the initial and pre-surgical MRI scans. The results of NAXIVA showed that importantly no patients had disease progression, whilst seven of the 21 patients responded to axitinib, a positive trial with a 31.3% response rate.
Images shared by Professor Stewart demonstrate the success of this treatment in reducing tumour thrombus size, with one patient's tumour length reduced from 9.3cm to 5.2cm following neoadjuvant treatment with axitinib.
A secondary endpoint was the percentage change in surgical approach. An improvement in level of control of IVC/renal vein was observed in five of 17 patients. Two patients had a change of approach from planned open to performed minimally invasive surgery, with one patient also having a reduction in level of control. One patient had a significantly smaller incision. Overall, seven of 17 (41%) patients in NAXIVA benefitted from a less morbid operation than initially planned.
Professor Stewart concludes that NAXIVA showed neoadjuvant treatment with axitinib is effective, safe, and had no significant negatives. These positive results from NAXIVA pave the way to further neoadjuvant trials using the latest combination treatments in RCC.
Led by Professor Grant Stewart as Chief Investigator, NAXIVA is sponsored by the Common Services Agency and co-ordinated by the Scottish Clinical Trials Research Unit (SCTRU) in Edinburgh. The trial is funded by Pfizer Limited and endorsed by Cancer Research UK (CRUK).