Axitinib offers hope for improving renal cell cancer surgical outcomes

Prof. Grant Stewart (University of Cambridge, UK) reported that the tyrosine kinase inhibitor axitinib elicited a 31% response rate in a phase 2 clinical trial exploring its effect on venous tumour thrombus (VTT) in renal cell cancer (RCC) [1].

VTT is found in 4–15% of RCC cases and the associated surgery for VTT removal bears a high morbidity and mortality rate (5–15% risk of mortality). 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. The current study aimed to determine whether surgical outcomes could be improved by pre-surgical treatment with axitinib. It was hypothesised that axitinib may help to decrease the extent of the VTT, thereby necessitating less invasive surgery and potentially improving survival rates.

The NAXIVA trial (NCT03494816) was a single-arm, single-agent, open-label, phase 2, feasibility study that evaluated the response of VTT to axitinib in 21 patients (15 males and 6 females) with a median age of 69 years, who had either metastatic or non-metastatic, clear cell RCC with venous invasion. Blood, urine, and tissue samples provided biomarkers to evaluate treatment response. All patients were scheduled for nephrectomy and inferior vena cava (IVC) tumour thrombectomy following 8 weeks of receiving steadily increasing doses axitinib (if tolerated). The starting dose of axitinib was 5 mg, then 7 mg, and finally a proposed maximum dose of 10 mg. Follow-ups were scheduled for 6 and 12 weeks after surgery.

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 axitinib. At the end of the treatment period, 26.58% demonstrated a reduction in VTT extent.

The investigators also employed 4 secondary outcome measures: the percentage of change in VTT height; the percentage of patients with a change in surgical management strategy at week 9 as compared with week 1; complications delineated in accordance with the Clavien-Dindo classification scheme; and response rate as assessed using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. At week 9, VTT height showed a median reduction of 21.49% (SD, 27.60%). Of the 17 patients who progressed to surgery, 7 (41.1%) were able to undergo a less invasive surgical procedure, and 2 (11.7%) experienced complications graded as Clavien-Dindo ≥3. The response rate according to RECIST was 61.90% SD, 14.29% PR, and 9.52% PD.

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.

1. Stewart G. NAXIVA: A phase II neoadjuvant study of axitinib for reducing extent of venous tumour thrombus in clear cell renal cell cancer (RCC) with venous invasion. Abstract 275, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.

 

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Posted on 24 March 202118 June 2021