Tyrosine kinase inhibitor axitinib elicited a 31% response rate in a phase 2 clinical trial that explored its effect on venous tumor thrombus (VTT) in renal cell cancer (RCC) . VTT is found in 4–15% of RCC cases. The outcomes associated with extirpative surgery for VTT in RCC are poor, with only a 40–65% 5-year survival rate in non-metastatic RCC. Complication rates increase with the extent of the VTT. Dr. Grant D. Stewart (University of Cambridge, UK) and colleagues investigated whether surgical outcomes could be improved by pre-surgical treatment with axitinib. They speculated that axitinib may help to decrease the extent of the VTT, thereby necessitating less invasive surgery. The NAXIVA trial (NCT03494816) was a single-arm, phase 2 feasibility study that evaluated the response of VTT to axitinib in 21 patients who had either metastatic or non-metastatic clear-cell RCC. The primary endpoint was the percentage of patients who showed a decreased level of VTT extension in accordance with the Mayo classification scheme, following 8 weeks of treatment with steadily increasing doses of axitinib. At the end of the treatment period, 26.6% demonstrated an improvement in VTT in accordance with the Mayo classification system. Secondary outcomes were change in surgical approach and change in VTT height. Of the 17 patients who progressed to surgery, 6 (35.3%) were able to undergo a less invasive surgical procedure. VTT height showed a median reduction of 21.5%. The researchers concluded that the prospective data provided by the NAXIVA trial is positive. The use of axitinib prior to surgery for RCC could decrease VTT extension and thus enable a less invasive surgical approach. These changes have the potential to reduce the morbidity and mortality currently associated with extirpative surgery for VTT in RCC, as well as to increase survival time. Research is currently being conducted to identify predictors of response.
- Stewart G. NAXIVA: A phase II neoadjuvant study of axitinib for reducing extent of venous tumor thrombus in clear cell renal cell cancer (RCC) with venous invasion. ASCO Genitourinary Cancers Symposium, 11–13 February 2021.