High-risk early RCC may benefit from neoadjuvant avelumab plus axitinib

Results of the NeoAvAx trial indicated that the neoadjuvant combination of immune checkpoint inhibitor avelumab plus VEGF inhibitor axitinib has potential for patients with high-risk, non-metastatic, clear-cell renal cell carcinoma (RCC).

Five-year recurrence rates of 60% in patients with high-risk RCC following nephrectomy pose a clinical unmet need [1]. Antibodies targeting PD-1/PD-L1 combined with vascular endothelial growth factor (VEGF) inhibitors are a first-line standard of care for metastatic RCC [2]. Neoadjuvant use of these combinations may lead to downstaging and reduce the risk of recurrence.

The NeoAvAx study (NCT03341845) aimed to evaluate the efficacy and safety of neoadjuvant avelumab plus axitinib in patients with high-risk RCC. It is a single-arm, phase 2 trial of 12 weeks neoadjuvant avelumab/axitinib prior to nephrectomy. The study enrolled 40 patients with high-risk, non-metastatic, clear-cell RCC; 90% of the participants had at least a T3 stage disease or higher. The primary endpoint was partial response in the primary tumour in ≥25%. Secondary endpoints were disease-free survival (DFS), overall survival (OS), and safety. Biomarker analyses were compared on pre-treatment biopsy and nephrectomy samples from 34 patients. Dr Axel Bex (Netherlands Cancer Institute, the Netherlands) presented the results [3].

Twelve patients (30%) had a partial response of the primary tumour. Median primary tumour downsizing was 20% and median post-treatment vital tumour presence was 50%. At a median follow-up of 23.5 months, recurrence occurred in 13 (32%) patients at a median of 8 months and 3 died of disease. The median OS and median DFS had not yet been reached. Among patients with a partial response, 10 of 12 were disease-free at the study data cut-off. Patients who had a partial response had better survival compared with patients who did not have a partial response. However, due to low numbers, this difference is not statistically significant.

Postoperative adverse events occurred in 8 participants. There were no treatment-related surgery delays and no primary tumour progression. No new safety signals were observed with the neoadjuvant regimen as compared with previously reported safety data for axitinib and avelumab.

An exploratory analysis of biomarkers showed that patients with recurrence had lower CD8-positive densities after treatment compared with patients without recurrence. Spatial transcriptomics of post-treatment primary tumour tissue revealed focal intratumoural differences in immune signatures.

Based on the outcome of NeoAvAx, Dr Bex concluded that “the disease-free survival data are encouraging, supporting further evaluation, although currently there are no randomised neoadjuvant versus adjuvant immune checkpoint inhibitor trials or neoadjuvant versus adjuvant immune checkpoint/VEGFR-TKI combination trials in this setting.”

1. Dabestani S, et al. Eur Urol Focus. 2019;5:857–866.
2. Choueiri TK, et al. N Engl J Med 2021;384:829–841.
3. Bex A, et al. Efficacy, safety, and biomarker analysis of neoadjuvant avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx). Abstract 289, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202229 February 2024