Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC).

• DOI: 10.1200/jco.2019.37.15_suppl.e16079
• Publication Date: 2019-05-27T16:08:48Z
• Authors: Matthew Labriola; Jason Zhu; Rajan Gupta; Shannon McCall; Jennifer Jackson; James R White; Elizabeth Weingar...; Eric Kong; Peter Simone; Eniko Papp; Kelly Gerding; John Simmons; Daniel J. George; Tian Zhang
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

e16079 Background: ICIs have revolutionized treatment for mRCC; however there are limited predictive biomarkers response to ICIs. PD-L1 status is still controversial, demonstrating little utility in mRCC. TMB melanoma and non-small cell lung cancer (NSCLC), but has not been validated Here, we assess the correlations between with outcomes ICI Methods: 34 patients (pts) mRCC who had previously received at Duke Cancer Institute were identified. Tumor samples retrospectively evaluated using a Personal Genome Diagnostics Assay somatic variants across > 500 genes, as well microsatellite status. was tested via Dako 28-8 IHC assay. Deidentified clinical information extracted from medical record tumor based on RECIST criteria. Results: Pts grouped by overall following therapy into either progressive disease (“PD”, n = 18) or control group (“DC”, 16), defined stable disease, partial response, complete response. displayed range 0.36 12.24 mutations/Mb mean score of 2.83 muts/Mb, no significant difference PD DC groups (mean 3.01 muts/Mb vs. 2.63 p 0.05). 9 32 evaluable positive, 4 5 group. Notably, enrichment mutations genes affiliated DNA repair (including BRCA1, BRCA2, FANCA, FANCB, FANCG, FANCM, MSH3, MSH6, RAD50, RAD51C, RAD51D, RAD54B, RECQL4, SLX4; 0.0444). damage gene found 8/10 (80%) metastatic specimens 14/24 (58%) primary tumors. Conclusions: Overall, this cohort, neither nor correlated patient Furthermore, high significantly associated expression within samples. The higher frequency suggests potential use signature warranting future prospective studies. Further studies matched primary-metastatic would be beneficial determine if occur more frequently versus specimens.