Results of the NeoAvAx trial indicate that the neoadjuvant combination of avelumab plus axitinib has potential for use in 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 are 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 II 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 participants had at least a T3 stage disease and higher. The primary endpoint was partial response in the primary tumor in at least 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) presented the results.3

Key Findings

Twelve patients (30%) had a partial response of the primary tumor. Median primary tumor downsizing was 20% and median post-treatment vital tumor 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 three 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 partial response.

However, due to low numbers, this difference is not statistically significant. Postoperative adverse events occurred in eight participants. There were no treatment-related surgery delays and no primary tumor progression. There were no new safety signals with the neoadjuvant regimen as compared with previously reported safety data for axitinib and avelumab.

Encouraging Data

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 tumor tissue revealed focal intertumoral 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 randomized neoadjuvant versus adjuvant immune checkpoint inhibitor trials or neoadjuvant versus adjuvant immune checkpoint/VEGFR-TKI combination trials in this setting.”

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