Compared to sunitinib, a combination of avelumab plus axitinib improves progression-free survival in patients with advanced clear-cell renal cell carcinoma (RCC), reports a phase 3 randomized trial in The New England Journal of Medicine.
The industry-sponsored JAVELIN Renal 101 trial included 886 patients with previously untreated advanced RCC with a clear-cell component—the most common type of kidney cancer. Patients assigned to the intervention group received the immunotherapy drug avelumab plus the highly selective vascular endothelial growth factor (VEGF) receptor inhibitor axitinib. Those in the comparison group received the anti-VEGF agent sunitinib, which has been a standard treatment for advanced clear-cell RCC.
The two primary endpoints were progression-free and overall survival among the 560 patients whose tumors were positive for programmed cell death ligand 1 (PD-L1). Progression-free survival in the overall sample was also assessed, along with objective response and safety outcomes.
In the PD-L1–positive group, median progression-free survival was 13.8 months with the avelumab/axitinib combination compared to 7.2 months with sunitinib: hazard ratio (HR) 0.61 for disease progression or death. Avelumab plus axitinib had a similar advantage in the overall population: progression-free survival 13.8 versus 8.4 months, HR 0.69.
The avelumab/axitinib combination had a 55.2% objective response rate in PD-L1–positive patients, compared to 25.5% with sunitinib. There were 37 deaths in the avelumab/axitinib group (median follow-up 11.6 months) and 44 in the sunitinib group (median follow-up 10.7 months). In both groups, 99% of patients experienced adverse events, with more than 70% of events being grade 3 or higher.
In a previous phase 1b trial in patients with advanced clear-cell RCC, avelumab plus axitinib produced an objective response rate of 58% and a disease control rate of 78%, with better results in PD-L1–positive patients. The JAVELIN Renal 101 results show longer progression-free survival with first-line avelumab plus axitinib, compared to sunitinib.
The efficacy benefit is seen in patients with and without PD-L1–positive tumors and across prognostic risk groups. The researchers believe their findings support “at least additive if not synergistic effects of the VEGF tyrosine kinase inhibitor-immune checkpoint inhibitor combination” [Motzer RJ, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019; DOI: 10.1056/NEJMoa1816047].