Rini BI, et al. - In view of the observed antitumor activity of the combination of pembrolizumab and axitinib in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma, researchers investigated outcomes of these patients treated with pembrolizumab plus axitinib vs sunitinib. Outcomes suggest achievement of significantly longer overall survival and progression-free survival, in addition to a higher objective response rate, with pembrolizumab plus axitinib treatment than sunitinib treatment among patients with previously untreated advanced renal-cell carcinoma.

• Researchers performed an open-label, phase 3 trial including 861 patients with previously untreated advanced clear-cell renal-cell carcinoma.
• Patients were randomized to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients).
• Overall survival and progression-free survival in the intention-to-treat population were the primary end points.
• The objective response rate was the key secondary end point.
• Results from the protocol-specified first interim analysis were reported.

• After a median follow-up of 12.8 months, the pembrolizumab–axitinib group and the sunitinib group had 89.9% and 78.3% of patients, respectively, who were alive at 12 months (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P<0.0001).
• The pembrolizumab–axitinib group and the sunitinib group had median progression-free survival of 15.1 months and 11.1 months, respectively (hazard ratio for disease progression or death, 0.69; 95% CI, 0.57 to 0.84; P<0.001).
• The objective response rate of 59.3% (95% CI, 54.5 to 63.9) and 35.7% (95% CI, 31.1 to 40.4) was observed in the pembrolizumab–axitinib group and sunitinib group, respectively (P<0.001).
• Irrespective of programmed death ligand 1 expression, the International Metastatic Renal Cell Carcinoma Database Consortium risk groups (ie, favorable, intermediate, and poor risk) benefited using pembrolizumab plus axitinib.
• In 75.8% of patients in the pembrolizumab–axitinib group and in 70.6% in the sunitinib group, grade 3 or higher adverse events were evident.