Hyung-Don Kim1, Min-Hee Ryu1, Young Soo Park2, Sun Young Lee3, Meesun Moon1, Yoon-Koo Kang4. 1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. 2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Asan Medical Center, Asan Institute for Life Science, University of Ulsan College of Medicine, Seoul, Republic of Korea. 4. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. ykkang@amc.seoul.kr.
Abstract
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.
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.
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