Dr Rini on a Biomarker Analysis for Pembrolizumab/Axitinib in Advanced RCC

Brian I. Rini, MD, FASCO, Ingram Professor of Medicine, Department of Medicine, Division of Hematology Oncology, Vanderbilt University, discusses findings from an exploratory biomarker analysis of the phase 3 KEYNOTE-426 study (NCT02853331) evaluating pembrolizumab (Keytruda) plus axitinib (Inlyta) vs sunitinib (Sutent) for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

To conduct the biomarker analysis, investigators used RNA sequencing to evaluate high or low expression of genes, Rini begins. Investigators also analyzed based on the presence of VHL, PBRM1, SETD2, and BAP1 DNA alterations, he adds. Furthermore, Rini and colleagues examined PD-L1 combined positive score (CPS), he says. During the analysis, investigators compared outcomes based on biomarker status both within individual arms and across arms, Rini notes.

Findings presented at the 2024 ASCO Annual Meeting showed that T-cell–inflamed gene expression profile (GEP) was associated with improved clinical outcomes within the pembrolizumab plus axitinib arm. Rini notes that the GEP test has been utilized in other solid tumors, such as non–small cell lung cancer and melanoma, before being utilized here in RCC. Unsurprisingly, patients with more inflamed tumors had improved outcomes with the immunotherapy-based combination, he says.

Conversely, higher angiogenesis was linked to improved clinical outcomes within the sunitinib arm. However, PD-L1 expression via CPS was negatively associated with overall survival in the sunitinib arm. Rini notes that this has been shown previously for sunitinib in RCC; however, he cautions that PD-L1 overall is a poor biomarker in kidney cancer. Although there is heterogeneity in PD-L1 expression in RCC, he says that it has not proved to be reliable for predicting outcomes in this patient population.

Additionally, improved overall response rates (ORRs) were observed for pembrolizumab plus axitinib compared with sunitinib across subsets of patients with various molecular subtypes. In the experimental arm, pembrolizumab plus axitinib produced the highest ORR among patients with the immune/proliferative subtype. In the sunitinib arm, the ORR was highest in patients within the angiogenic subtype.