The ASCO-GU 2019 brought exciting new insights into renal cell carcinoma: The combination of pembrolizumab and axitinib provided longer overall survival and progression-free survival with a high response rate in patients with non-pretreated mRCC.
The 5-year survival of advanced or metastatic clear cell renal cell carcinoma (mccRCC) is generally only 12%. Despite some progress in RCC therapy, e.g. through the introduction of checkpoint inhibitors, the orbital potential of this tumor entity remains limited.
The results of the phase III trial KEYNOTE-426, which was presented at this year's ASCO-GU congress, were all the more expected. For the study, 861 patients with clear cell mRCC without prior systemic therapy were randomized to two treatment groups. The first group then received pembrolizumab (200 mg intravenously every 3 weeks, up to 35 cycles) in combination with axitinib (5 mg orally, 2x daily). The second group was treated with the therapy standard SUN (sunitinib) (50 mg oral, 1x daily). The study authors considered overall survival (OS) and progression-free survival (PFS) to be the primary endpoints.
The mean follow-up time was 12.8 months. The results of the study showed that both OS and PFS saw further improvements in combination therapy than SUN. The OS rate after 12 months was 89.9% in the combined arm, whereas only 78.3% could be achieved with SUN (HR= 0.53; p < 0.0001). The mean PFS in the arm with pembrolizumab and axitinib was also higher than with the therapy standard SUN (HR = 0.69; p = 0.0001). The objective response rate (ORR) in the combined arm was 59.3%, and SUN only of 35.7%.
The advantage offered by the combination of pembrolizumab and axitinib was independent of the risk group and PD-L1 status.
Powles T et al. pembrolizumab (pembro) plus axitinib (axi) versus SUN as first-line therapy for locally advanced or metastatic renal cell carcinoma (mRCC): phase III KEYNOTE-426 study. ASCO-GU 2019