Pembrolizumab/axitinib is approved as a first-line treatment for metastatic renal cell carcinoma (mRCC), but its safety and efficacy in later lines of therapy has not been researched. When used as a first-line treatment, the drug combination has demonstrated superior progression free survival (PFS), objective response rate (ORR), and overall survival compared with sunitinib.
Dizman et al examined clinical data of patients with mRCC who had received pembrolizumab/axitinib in the second line or beyond to determine its effectiveness. Data were collected from Yale New Haven Hospital in Connecticut. Kaplan-Meier function was used to analyze survival, and best objective response was assessed using RECIST 1.1 criteria.
The research team analyzed data from 38 patients with a median age of 64 years. A total of 92.1% of patients had clear cell mRCC, while 18.4% had sarcomatoid dedifferentiation. A total of 94.7% of patients had received prior immune checkpoint inhibitors (ICI), and 39.5% had received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-R-TKI).
Pembrolizumab/axitinib was administered as a second-line therapy in 21 (55.5%) patients, as a third-line therapy in 5 (13.2%) patients, and beyond in 12 (30.2%). At a median follow-up of 17.1 months, the median PFS was 9.7 months (95% CI, 4.1-15.3 months). Out of 36 response evaluable patients, the ORR was 25.0%, and the disease control rate (including stable disease for at least 6 months) was 66.6%.
The most common treatment among patients was first-line nivolumab/ipilimumab followed by second-line pembrolizumab/axitinib (n=17, 44.7%). In this cohort, median PFS with pembrolizumab/axitinib was 11.1 months (95% CI, 8.4-13.7 months), with an ORR of 31.4%. Adverse events (AEs) occurred in 86.8% of patients, with grade 3-4 AEs attributed to pembrolizumab and axitinib seen in 18.4% and 6.4% of patients, respectively.
The combination treatment of pembrolizumab/axitinib in previously treated patients with mRCC showed activity and demonstrated AE rates comparable with those reported in the first line. Further studies to evaluate ICI-VEGF-R-TKI combinations beyond first-line treatment are needed to determine the best treatment sequencing for mRCC.
