The randomized, open-label, phase 3 KEYNOTE-426 study has demonstrated that Pembrolizumab ( Keytruda ) + Axitinib ( Inlyta ) significantly improved overall survival ( OS ), progression-free survival ( PFS ), and objective response rate ( ORR ) versus Sunitinib ( Sutent ) as first-line therapy for advanced renal cell carcinoma ( aRCC ) at the first pre-planned interim analysis ( minimum study follow-up of 7 months ).
Researchers have presented updated analyses.
Treatment-naive patients with clear cell advanced renal cell carcinoma, KPS greater than or equal to 70%, and measurable disease ( RECIST v1.1 ) were randomly assigned 1:1 to receive Pembrolizumab 200 mg IV Q3W ( every 3 weeks ) for up to 35 doses + Axitinib 5 mg orally BID ( twice a day ) or Sunitinib 50 mg orally QD ( once daily ) on a 4-weeks on / 2-weeks off schedule until progression, toxicity, or withdrawal.
Randomization was stratified by IMDC risk ( favorable versus intermediate vs poor ) and geographic region ( North America vs Western Europe vs rest of world ).
Primary end points were overall survival and progression-free survival. Secondary end points were , objective response rate, duration of response ( DOR ), and safety.
A post-hoc exploratory analysis was done to evaluate association of depth of response ( maximum reduction from baseline in sum of diameters of target lesions ) and overall survival using landmark analysis up to 6 months after randomization.
861 patients were randomly assigned ( Pembrolizumab + Axitinib, n=432; Sunitinib, n=429 ).
Median ( range ) duration of follow-up for all patients was 27.0 months ( 0.1-38.4 ).
Pembrolizumab + Axitinib improved overall survival ( hazard ratio, HR=0.68 [ 95% CI, 0.55-0.85 ]; P less than 0.001; 24-months OS rate, 74% vs 66% ) versus Sunitinib.
Median ( 95% CI ) overall survival was not reached with Pembrolizumab + Axitinib and was 35.7 months ( 33.3-NR ) with Sunitinib.
Pembrolizumab + Axitinib improved progression-free survival ( HR=0.71 [ 95% CI, 0.60-0.84 ]; P less than 0.001; 24-months PFS rate, 38% vs 27% ) vs Sunitinib.
For Pembrolizumab + Axitinib versus Sunitinib respectively, median ( 95% CI ) progression-free survival was 15.4 ( 12.7-18.9 ) vs 11.1 months ( 9.1-12.5 ); ORR was 60% vs 40% ( P less than 0.0001 ); complete response ( CR ) rate was 9% vs 3%; and median duration of response ( DOR ) was 23.5 months ( range 1.4+ to 34.5+ ) vs 15.9 months ( range 2.3-31.8+ ).
In general, Pembrolizumab + Axitinib benefit was observed in all subgroups tested, including IMDC risk and PD-L1 expression subgroups.
Post-hoc landmark analysis at 6-months showed that patients on Pembrolizumab + Axitinib with 80% or more target lesion reduction had overall survival similar to that of patients with complete response per RECIST v1.1 based on Kaplan-Meier curves and HR [ 95% CI ] estimates ( 0.20 [ 0.05-0.84 ] vs. 0.10 [ 0.01-0.76 ], respectively ) versus patients with 0-30% target lesion reduction.
No new safety signals were observed.
In conclusion, Pembrolizumab + Axitinib continued to demonstrate superior and durable antitumor activity versus Sunitinib in patients with first-line aRCC with a 27-months median follow up. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020