Insertion–deletion rate is a qualitative aspect of the tumor mutation burden associated with the clinical outcomes of gastric cancer patients treated with nivolumab

• Published in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 25; no. 1; pp. 226 - 234
• Main Authors: Kim, Hyung-Don, Ryu, Min-Hee, Park, Young Soo, Lee, Sun Young, Moon, Meesun, Kang, Yoon-Koo
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 2022; Springer Nature B.V
• Subjects: Abdominal Surgery; B7-H1 Antigen - genetics; Biomarkers, Tumor - genetics; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Clinical outcomes; Gastric cancer; Gastroenterology; Gene deletion; Humans; Immunotherapy; Insertion; Lung Neoplasms - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Mutation; Nivolumab - adverse effects; Nivolumab - therapeutic use; Oncology; Original Article; Patients; Population studies; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Surgical Oncology; Survival; Targeted cancer therapy; Tumors; Insertion and deletion; Immune checkpoint inhibitor; Gastric cancer; Nivolumab; Tumor mutation burden
• ISSN: 1436-3291; 1436-3305
• DOI: 10.1007/s10120-021-01233-1

Background We aimed to investigate the clinical implications of the tumor mutation burden (TMB) and insertion–deletion (indel) rate in gastric cancer patients treated with nivolumab. Methods A total of 105 patients with advanced gastric cancer who were treated with nivolumab as third or later line of therapy were included as the study population. The indel rate was defined as the proportion of indels making up the TMB. Results The median age was 58 (32–78 years), and 65 (61.9%) were men. Patients with TMB > 18.03/Mb showed superior progression-free survival (PFS) and overall survival (OS) compared to those with TMB ≤ 18.03/Mb. Patients with a high indel rate (> 40%) had a favorable PFS and OS compared to those with a lower indel rate (≤ 40%) ( P  = 0.009 and P  = 0.007, respectively). The association between a high indel rate and favorable PFS and OS was prominent in a subgroup with TMB > 18.03/Mb ( P  < 0.001 and P  = 0.007 for PFS and OS, respectively), but not in that with TMB ≤ 18.03/Mb. All five patients with deficient-MMR fell into the category of ‘TMB > 18.03/Mb with an indel rate of > 40%. TMB ≥ 18.03/Mb with an indel rate of > 40% was independently associated with a favorable PFS (hazard ratio [HR] 0.07, P  = 0.012) and OS (HR 0.09, P  = 0.023). Conclusion TMB and indel rate should be jointly considered to better predict survival outcomes of gastric cancer patients treated with nivolumab. Our findings deserve further investigation and validation in future studies.