Subsequent therapy following pembrolizumab plus axitinib or sunitinib treatment for advanced renal cell carcinoma (RCC) in the phase III KEYNOTE-426 study

Abstract

Background:In the phase III KEYNOTE-426 study, pembrolizumab + axitinib showedsignificant improvement in OS, PFS, and ORR vs sunitinib in patients with RCC. Thisanalysis assessed subsequent treatment in patients enrolled in KEYNOTE-426.Methods:Treatment-naive patients with clear cell RCC, KPS score =70%, andmeasurable disease (RECIST v1.1) were randomly assigned 1:1 to receive pem-brolizumab 200 mg IV every 3 weeks for up to 35 doses + axitinib 5 mg orally twicedaily or sunitinib 50 mg once daily (4 weeks on/2 weeks off) until progression, toxicity,or withdrawal. Type of and time to subsequent therapy were assessed.Results:Of patients in the pembrolizumab + axitinib arm and in the sunitinib arm,81.4% (349/432) and 90.6% of patients (385/429), respectively, discontinued treat-ment; radiologic or clinical PD was the most common reason for discontinuation inboth (pembrolizumab + axitinib: 65.0% [227/349]; sunitinib: 68.1% [262/385]). Ofpatients who discontinued, 58.5% of patients (204/349) in the pembrolizumab +axitinib arm and 73.0% (281/385) in the sunitinib arm received subsequent therapy(Table). Although a similar proportion of patients in both arms received subsequenttherapy with a VEGF/VEGFR inhibitor (pembrolizumab + axitinib: 88.2% [180/204];sunitinib: 68.7% [193/281]), a greater proportion of patients in the sunitinib arm(74.4% [209/281]) received subsequent PD-1/PD-L1 inhibitor therapy than in thepembrolizumab + axitinib arm (21.6% [44/204]). Of patients in the pembrolizumab +axitinib arm and the sunitinib arm, 32.4% (66/204) and 22.8% (64/281), respectively,received other therapies.Conclusions:The superior efficacy of pembrolizumab + axitinib compared withsunitinib is observed despite the increased use of subsequent therapy in the sunitinibarm. These data continue to support the use offirst-line pembrolizumab + axitinib in patients with RCC