The mutational burden of targeted genes significantly correlated with overall survival after targeted therapy in metastatic renal cell carcinoma.

Abstract

643 Background: This study aimed to find the correlation between tumor mutation burden and systemic first line therapeutic response in metastatic tissue samples from patients with metastatic renal cell carcinoma (mRCC). Methods: Between 2005 and 2017, 168 triplet-tissue block samples from 56 mRCC patients were selected for targeted gene sequencing (TGS) using the 88 targeted genes from the National Cancer Center, Korea (NCC) kidney cancer panel. The patients’ medical records, including therapeutic responsive profiles with overall survival (OS) to first-line targeted therapy, were evaluated with the mutational burden of triplet tissue samples using 88 TGS. A few significant target genes associated with therapeutic response towards targeted therapy were identified after comparing the mutational burden of positive for all three blocks and one or two positive blocks (p-value < 0.05). Results: The median PFS for the first-line targeted therapy and OS were 8.7 and 42 months, respectively. MSKCC and Heng risk criteria showed 28.9/65.8/5.3% and 26,3/57.9/15.8% for favorable, intermediate, and poor risk groups, respectively. Also, 55.3% and 52.6% patients received metastatectomy and nephrectomy, respectively. Eighteen (32.1%) patients had all triplet blocks passed for quality check, whereas 21 (37.5%) and 17 (30.4%) patients had two or one passed tissue blocks, respectively. Among the 18 patients with triplet-block, TP53, URB4, PTK2, and SGO2 genes had significant discrimination power for OS on comparing their mutational burden in the three blocks positive group (N = 7) and two or fewer blocks positive groups (N = 11) (p < 0.05). Among the 39 patients with either doublet or triplet blocks passed for quality check, TP53, URB1, PTK2, SGO2, BRAF, NEDD4, PDXDC1, CDH1, FGFR2, RET, RUNX1, and SDHB genes had significant discrimination power for DFS when comparing their mutational burden in the three blocks positive group (N = 7) and two or fewer blocks positive groups (N = 14) (p < 0.01). Conclusions: The study showed the tumor mutational burden of many vital targeted genes to be significantly correlated with OS from metastatic tissues in mRCC.