Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma

•Avelumab plus axitinib significantly prolonged progression-free survival versus sunitinib in advanced renal cell carcinoma. •Although overall survival data were immature, results favored the combination over sunitinib across prespecified subgroups. •Adjusting for subsequent use of PD-1/PD-L1 inhibitors in the sunitinib arm predicted a survival benefit for the combination. •Among all randomized patients, avelumab plus axitinib had a longer mean duration of response than sunitinib. •Avelumab plus axitinib prolonged progression-free survival on next-line therapy versus sunitinib. BackgroundThe phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. Patients and methodsTreatment-naive patients with aRCC were randomized (1: 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1–positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. ResultsOf 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm PD-L1+ population: hazard ratio (HR) 0. 62 95% confidence interval (CI) 0. 490–0. 777; one-sided P < 0. 0001; median 13. 8 (95% CI 10. 1–20. 7) versus 7. 0 months (95% CI 5. 7–9. 6) ; overall population: HR 0. 69 (95% CI 0. 574–0. 825) ; one-sided P < 0. 0001; median 13. 3 (95% CI 11. 1–15. 3) versus 8. 0 months (95% CI 6. 7–9. 8) ]. OS data were immature PD-L1+ population: HR 0. 828 (95% CI 0. 596–1. 151) ; one-sided P = 0. 1301; overall population: HR 0. 796 (95% CI 0. 616–1. 027) ; one-sided P = 0. 0392. ConclusionAmong patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature. Clinical Trial numberNCT02684006. The phase 3 JAVELIN Renal 101 trial (NCT02684006) demonstrated significantly improved progression-free survival (PFS) with first-line avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma (aRCC). We report updated efficacy data from the second interim analysis. Treatment-naive patients with aRCC were randomized (1: 1) to receive avelumab (10 mg/kg) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were PFS and overall survival (OS) among patients with programmed death ligand 1–positive (PD-L1+) tumors. Key secondary end points were OS and PFS in the overall population. Of 886 patients, 442 were randomized to the avelumab plus axitinib arm and 444 to the sunitinib arm; 270 and 290 had PD-L1+ tumors, respectively. After a minimum follow-up of 13 months (data cut-off 28 January 2019), PFS was significantly longer in the avelumab plus axitinib arm than in the sunitinib arm PD-L1+ population: hazard ratio (HR) 0. 62 95% confidence interval (CI) 0. 490–0. 777; one-sided P < 0. 0001; median 13. 8 (95% CI 10. 1–20. 7) versus 7. 0 months (95% CI 5. 7–9. 6) ; overall population: HR 0. 69 (95% CI 0. 574–0. 825) ; one-sided P < 0. 0001; median 13. 3 (95% CI 11. 1–15. 3) versus 8. 0 months (95% CI 6. 7–9. 8) ]. OS data were immature PD-L1+ population: HR 0. 828 (95% CI 0. 596–1. 151) ; one-sided P = 0. 1301; overall population: HR 0. 796 (95% CI 0. 616–1. 027) ; one-sided P = 0. 0392. Among patients with previously untreated aRCC, treatment with avelumab plus axitinib continued to result in a statistically significant improvement in PFS versus sunitinib; OS data were still immature.