Correlates of clinical benefit from immunotherapy and targeted therapy in metastatic renal cell carcinoma: comprehensive genomic and transcriptomic analysis

BACKGROUND: mutations and response with immunotherapy (IO). We sought to determine genomic predictors of differential response to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) and IO. METHODS: Consecutive patients who underwent genomic profiling were identified; patients receiving either VEGF-TKIs or IO were included. Clinical tumor-normal whole exome sequencing and tumor whole transcriptome sequencing test were performed using a Clinical Laboratory Improvement Amendments (CLIA)-certified assay (Ashion Analytics; Phoenix, Arizona, USA). Genomic findings were compared between patients with clinical benefit (CB; complete/partial response or stable disease for >6 months) and no clinical benefit (NCB) in VEGF-TKI-treated patient cohort and IO-treated patient cohort. RESULTS: mutations were more prevalent in patients with CB with IO and VEGF-TKIs, no statistically significant association was found. CONCLUSIONS: loss-of-function mutations.