Tumor Mutational Burden as a Biomarker for Advanced Biliary Tract Cancer

• Published in: Technology in cancer research & treatment 2021, Vol.20, p.15330338211062324-15330338211062324
• Main Authors: Kim, Hongsik, Kim, Hana, Kim, Ryul, Jo, Hyunji, Kim, Hye Ryeon, Hong, Joohyun, Park, Joon Oh, Park, Young Suk, Kim, Seung Tae
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bile Duct Neoplasms - diagnosis; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - mortality; Bile Duct Neoplasms - therapy; Biliary tract; Biomarkers; Biomarkers, Tumor; Biopsy; Cancer; Cholangiocarcinoma; Cisplatin; Combined Modality Therapy; Disease control; Disease Management; Disease Susceptibility; Gemcitabine; Gene Expression Profiling; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Immune checkpoint inhibitors; Immunotherapy; Kaplan-Meier Estimate; Mutation; Neoplasm Grading; Neoplasm Staging; Next-generation sequencing; Original; Patients; Prognosis; Treatment Outcome; Tumors
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/15330338211062324

Background: High tumor mutational burden (TMB-H) has been reported as a predictive marker to immunotherapy or prognostic marker in various tumor types. However, there has been little study of the role of TMB-H in advanced biliary tract cancer (BTC). Methods: We analyzed 119 advanced BTC patients who received Gemcitabine/Cisplatin (GP) as a first-line treatment between November 2019 and April 2021. Next-generation sequencing (NGS), including TMB analysis, as a routine clinical practice was performed in 119 patients. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. Results: Among 119 patients, 18 (18.5%) had a tumor with high TMB (≥ 10 Muts/Mb). There were no significant differences between the status of TMB and clinical outcomes with GP, including objective response rate (ORR) (P = .126), disease control rate (DCR) (p = .454), and median progression-free survival (PFS) (p = .599). The median overall survival (OS) was not different between patients with TMB-H and no TMB-H (p = .430). In subgroup analysis of 32 patients receiving immune checkpoint inhibitor (ICIs), there were significant differences in ORR (p = .034) and median PFS (p = .025) with ICIs between patients with and without TMB-H. Conclusions: This study revealed that TMB-H in advanced BTCs did not have a prognostic or role in the standard first-line treatment. However, TMB-H might be a predictive biomarker for response to ICIs in advanced BTC.