Prior results of the JAVELIN Renal 101 trial at a minimum follow-up of 13 months demonstrated a median progression-free survival (PFS) benefit with avelumab plus axitinib compared to sunitinib in previously untreated patients with advanced renal cell carcinoma (aRCC) with PD-L1-positive tumours (HR[95% CI]: 0.62[0.49-0.78]).1 No benefit was seen in overall survival (OS) in the PD-L1-positive or intent-to-treat population.1 The combination of avelumab plus axitinib is currently not recommended in the first-line setting by the EAU and ESMO guidelines.2,3 Longer follow-up data (minimal follow-up of 68 months) were recently published, including the primary analysis of OS.4
METHODS
The phase III JAVELIN Renal 101 randomised 886 previously untreated patients with aRCC to avelumab plus axitinib vs sunitinib. Primary endpoints were OS and PFS in the PD-L1-positive population.
RESULTS
After a minimum follow-up of 68 months, median OS was 43.2 months with avelumab plus axitinib compared to 36.2 months with sunitinib in the PD-L1-positive population (HR[95% CI]: 0.86[0.70-1.06], p= 0.0755), and 44.8 months vs 38.9 months, respectively, in the overall population (HR[95% CI]: 0.88[0.75-1.04], p= 0.0669). Investigator-assessed PFS remained prolonged with avelumab plus axitinib compared to sunitinib, with 5-year PFS rates of 13.4% vs 3.6% in the PD-L1-positive population (HR[95% CI]: 0.57[0.47-0.70]) and 12.0% vs 4.4% in the overall population (HR[95% CI]: 0.66[0.57-0.77]). The objective response rate (ORR) in the overall population was 59.7% with avelumab plus axitinib vs 32.0% with sunitinib. Duration of response ≥5 years was observed in 16.4% of patients receiving avelumab plus axitinib vs 9.2% with sunitinib. Rates of grade ≥3 treatment-related adverse events were 66.8% with avelumab plus axitinib and 61.5% with sunitinib.
CONCLUSIONS
The JAVELIN Renal 101 trial provides the longest follow-up to date for an immune checkpoint inhibitor and tyrosine kinase inhibitor combination in aRCC. Although OS numerically favoured avelumab plus axitinib over sunitinib, the difference was not statistically significant. Avelumab plus axitinib demonstrated sustained efficacy benefits vs sunitinib, including prolonged PFS, higher ORR, and more durable responses, with a manageable long-term safety profile.
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