Abstract
BACKGROUND: In the phase III JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) versus sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS). PATIENTS AND METHODS: Patients with untreated aRCC (any prognostic risk score) were enrolled. The primary endpoints were OS and PFS in the programmed death-ligand 1-positive (PD-L1+) population. ORR, duration of response, safety, and patient-reported outcomes (PROs) were also assessed. RESULTS: The minimum follow-up was 68 months in all patients. The median OS with avelumab + axitinib versus sunitinib, respectively, was 43.2 months [95% confidence interval (CI) 36.5-51.7 months] versus 36.2 months (95% CI 29.8-44.2 months) in the PD-L1+ population [hazard ratio (HR) 0.86 (95% CI 0.701-1.057); P = 0.0755] and 44.8 months (95% CI 39.7-51.1 months) versus 38.9 months (95% CI 31.4-45.2 months) in the overall population [HR 0.88 (95% CI 0.749-1.039); P = 0.0669]. Investigator-assessed PFS remained prolonged with avelumab + axitinib versus sunitinib [5-year event-free rate in the overall population, 12.0% (95% CI 8.9% to 15.6%) versus 4.4% (95% CI 2.5% to 7.3%)]. ORR in the overall population was 59.7% (95% CI 55.0% to 64.3%) with avelumab + axitinib versus 32.0% (95% CI 27.7% to 36.5%) with sunitinib; duration of response was ≥5 years in 16.4% (95% CI 12.0% to 21.4%) versus 9.2% (95% CI 4.6% to 15.7%), respectively. Rates of grade ≥3 treatment-related adverse events were 66.8% versus 61.5%, respectively. PROs were similar between arms. CONCLUSIONS: JAVELIN Renal 101 provides the longest follow-up to date for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase III trial in aRCC. OS analyses favored avelumab + axitinib versus sunitinib but did not reach statistical significance; subsequent treatment may have impacted results. Avelumab + axitinib provided long-term efficacy benefits versus sunitinib, including prolonged PFS, a nearly doubled ORR, and more durable responses, with a manageable long-term safety profile.