The predicting role of circulating tumor DNA landscape in gastric cancer patients treated with immune checkpoint inhibitors

Molecular Cancer

Yu-Ming Ouyang¹  Dong-Qin Zhu¹  Yang Shao²  Chao-pin Yang³  Jin-qi You³  Hui-Yan Luo⁴  Feng-Hua Wang⁴  Dong-Sheng Zhang⁴  Rui-Hua Xu⁴  Dong-Liang Chen⁴  Feng Wang⁴  Zhi-Qiang Wang⁴  Yu-Hong Li⁴  Ying Jin⁴  Xu-Xian Chen⁵  Jin-Sheng Huang⁵ 

[1]Medical Department, Nanjing Geneseeq Technology Inc., 210032, Nanjing, Zhejiang, China

[2]Medical Department, Nanjing Geneseeq Technology Inc., 210032, Nanjing, Zhejiang, China

[3]School of Public Health, Nanjing Medical University, 211166, Nanjing, Zhejiang, China

[4]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, 510060, Guangzhou, P. R. China

[5]Department of Biotherapy, Sun Yat-sen University Cancer Center, 510060, Guangzhou, Guangdong, China

[6]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, 510060, Guangzhou, P. R. China

[7]Department of Medical Oncology, Sun Yat-sen University Cancer Center, 510060, Guangzhou, Guangdong, China

[8]State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, 510060, Guangzhou, P. R. China

[9]Department of VIP region, Sun Yat-sen University Cancer Center, 510060, Guangzhou, Guangdong, China

关键词: Circulating tumor DNA;    Immune checkpoint inhibitors;    Gastrointestinal cancer;    Advanced;    Biomarkers;   

DOI  :  10.1186/s12943-020-01274-7

来源: Springer

【 摘 要 】

A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p < 0.05). Patients with alterations in CEBPA, FGFR4, MET or KMT2B (p = 0.09) gene had greater likelihood of immune-related adverse events (irAEs). ctDNA can serve as a potential biomarker of the response to immunotherapy in advanced gastric cancers, and its potential role in predicting irAEs worth further exploration.

【 授权许可】

CC BY