Abstract 1419P
Background
We aimed to investigate the clinical implications of the tumor mutation burden (TMB) and insertion-deletion (Indel) burden in gastric cancer patients treated with nivolumab.
Methods
A total of 105 patients with advanced gastric cancer who were treated with nivolumab as 3rd or later line of therapy were included as the study population. The TMB was determined based on a panel sequencing platform as the sum of the number of single-nucleotide variations and Indels per megabases in target lesion (Mb). The Indel rate was defined as the proportion of Indels making up the TMB. The mismatch repair (MMR) status and PD-L1 combined positive score (CPS) were assessed by immunohistochemistry.
Results
The median age was 58 (range 32-78 years), and 65 patients (61.9%) were men. Patients with TMB ≥ 10/Mb showed similar progression-free survival (PFS) and overall survival (OS) compared to those with TMB < 10/Mb (P = 0.320 and P = 0.140, respectively). Patients with a high Indel rate (> 40%) had favorable PFS and OS compared to those with a lower Indel rate (≤ 40%) (P = 0.009 ad P = 0.007, respectively). The association between a high Indel rate and a favorable PFS and OS was prominent in a subgroup with TMB ≥ 10/Mb (P < 0.001 and P = 0.002 for PFS and OS, respectively), but not in that with TMB < 10/Mb. All five patients with deficient-MMR fell into the category of ‘TMB ≥ 10/Mb with an Indel rate of > 40%. TMB ≥ 10/Mb with an Indel rate of > 40% and PD-L1 CPS ≥ 1 were independently associated with a favorable PFS (hazard ratio [HR] 0.08, 95% confidence interval [CI] 0.01-0.59, P = 0.013 and HR 0.45, 95% CI 0.24-0.85, P = 0.015, respectively) and OS (HR 0.11, 95% CI 0.01-0.90, P = 0.040 and HR 0.42, 95% CI 0.21-0.86, P = 0.017, respectively).
Conclusions
The Indel rate represents a qualitative aspect of TMB associated with favorable clinical outcomes in gastric cancer patients treated with nivolumab. Our findings deserve further investigation and validation in future studies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Kang: Other, Personal, Advisory Role: ALX Oncology; Other, Personal, Advisory Role: Amgen; Other, Personal, Advisory Role: BMS; Other, Personal, Advisory Role: Blueprint; Other, Personal, Advisory Role: Daehwa; Other, Personal, Advisory Role: Macrogenics; Other, Personal, Advisory Role: Merck (MSD); Other, Personal, Advisory Role: Novartis; Other, Personal, Advisory Role: Surface Oncology; Other, Personal, Advisory Role: Zymeworks. All other authors have declared no conflicts of interest.