The extent of venous tumor thrombus (VTT) occurs in 4-15% of cases of renal cell carcinoma (RCC). Mayo’s classification distinguishes four levels of VTT extension between the renal vein and the supradiaphragmatic inferior vena cava (IVC). Although surgery is performed with a curative intention, mortality is high (5-15%) and complications may increase according to the level of VTT
Five-year survival rates for patients with renal cell carcinoma (RCC) and venous tumor thrombus (VTT) are low, reaching approximately 40%-65% in the non-metastatic setting. During the 2021 Genitourinary Cancers Symposium, NAXIVA (NCT03494816) was presented, a trial that evaluated the response of renal cell carcinoma (RCC) with venous tumor thrombus (VTT) to axitinib. The researchers’ hypothesis is that neoadjuvant targeted therapy may reduce the phase of VTT, surgical morbidity and mortality, resulting in better survival.
This is a multicenter, phase II, single-arm, single-agent study that evaluated the efficacy of axitinib in patients with metastatic and non-metastatic clear cell renal cell carcinoma (ccRCC) prior to nephrectomy and thrombectomy. In all, 21 people were recruited over a 24-month period – between 15 December 2017 and 6 January 2020 – at five locations in the UK. They received therapy for eight weeks with axitinib (initial dose of 5 mg 2x per day, increasing to 10 mg 2x daily as tolerated) before planned surgery.
The primary outcome was the percentage of evaluable patients with an improvement in VTT, according to Mayo’s classification (assessed by abdominal magnetic resonance imaging at screening and at week 9, before surgery). Secondary outcomes included the percentage change in surgical approach, the extension of VTT, response rate and assessment of surgical morbidity by clavien-dindo classification.
The percentage of evaluable patients with an improvement in VTT, according to Mayo’s classification, was 26.58%. In addition, 35.29% had a change in the surgical approach to a less invasive option. There was a median percentage reduction in the extent of VTT of 21.49%.
The response rate by RECIST in the evaluable population was 61.90% for stable disease, 14.29% for partial response, and 9.52% for disease progression. In terms of surgical morbidity, 11.76% experienced Clavien-Dindo 3 or major complications (0 CD3, 1 CD4, 1 CD5).
The authors conclude that NAXIVA provides unique prospective data on the feasibility of administering neoadjuvant axitinib to decrease the phase of VTT in the inferior vena cava, reducing the extent of surgery.
Stewart GD, et al. 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. Abstract 275. 2021 Genitourinary Cancers Symposium. DOI:10.1200/JCO.2021.39.6_suppl,275