Elizabeth Plimack, MD @FoxChaseCancer gives an updated analysis of KEYNOTE-426 at ASCO 2020 Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced renal cell carcinoma (RCC)
The randomized, open-label, phase 3 research KEYNOTE-426 (NCT02853331) showed that pembrolizumab (pembro) + axitinib (axi) significantly improved OS, PFS, and ORR vs. sunitinib as first-line therapy for advanced RCC (aRCC) in the first pre-planned interim review (minimum follow-up research of 7 mo). Updated analysis as seen here.
Treatment-naive patients (pts) with clear cell aRCC, KPS approximately 70%, and detectable disease (RECIST v1.1) were randomly allocated to receive pembro 200 mg IV Q3W for up to 35 doses + axi 5 mg orally BID or sunitinib 50 mg orally QD on a 4-wk on/2-wk off schedule before escalation, toxicity, or withdrawal. IMDC probability (favorable vs. good vs. poor) and geographical area (North America vs. Western Europe vs. the rest of the world) have stratified randomisation. OS and PFS were the main endpoints. ORR, DOR and Safety were secondary endpoints. All values for P are zero. A post-hoc exploratory analysis was performed to determine the relationship of response depth (maximum reduction from baseline in amount of target lesion diameters) and OS using landmark analysis up to 6 mo after randomisation.
861 pts were distributed at random (pembro + axi, n = 432; sunitinib, n = 429). The median follow-up time (range) for all points was 27.0 Mo (0.1-38.4). Pembro + axi enhanced OS (HR, 0.68 [95 % CI, 0.55-0.85]; P<0.001; 24-mo OS pace, 74% vs. 66%) vs. sunitinib. Median (95 per cent CI) OS with pembro+axi was not reached and sunitinib was 35.7 mo (33.3-NR). Pembro + axi enhanced PFS (HR, 0.71 [95 % CI, 0.60-0.84]; P < 0.001; 24-mo PFS pace, 38% vs 27%) vs sunitinib. For pembro + axi vs sunitinib, mean (95 % CI) PFS was 15.4 (12.7-18.9) vs 11.1 mo (9.1-12.5); ORR was 60% vs 40% (P < 0.0001); CR was 9% vs 3%; and median DOR was 23.5 mo (range 1.4 + to 34.5 +) vs 15.9 mo (range 2.3-31.8 +). In general, the gain pembro + axi was observed in all tested subgroups, including subgroups of IMDC risk and expression PD-L1. Based on Kaplan-Meier curves and HR [95 percent CI] estimates (0.20 [0.05-0.84] vs. 0.10 [0.01-0.76], respectively) vs. pts with 0-30 percent target lesion reduction, a post-hoc landmark study at 6-mo showed that pts on pembro+axis had OS comparable to pts with CR per RECIST v1.1 based on 0.20 [0.05-0.84] vs. 0.10 [0.01-0.76] estimates. No new protection feeds have been found.
Pembro + axi continued to display superior and long-lasting antitumor activity vs sunitinib in first-line aRCC pts with a 27-mo median follow-up; no new safety signals were noted. Details on clinical trials: NCT02853331.