Gastric cancer is classified by molecular subgroups, which include tumors with stable genomes, tumors with chromosomal instability, microsatellite unstable tumors, and tumors that are Epstein-Barr virus stable.1 Some patients with PD-L1–expressing, microsatellite unstable tumors, or Epstein-Barr virus-stable gastric tumors can be targeted for treatment with immune checkpoint inhibitors that improve antitumor activity and survival in these patient populations.1 Biomarkers can help assess if a person with cancer will respond to treatment and may indicate which treatment may be effective.2 These are being actively investigated in gastric cancer, including tumor mutational burden (TMB). Studies have demonstrated that high-TMB gastric cancer tumors have a survival advantage over those with low TMB.
At the 2021 European Society for Medical Oncology virtual meeting, researchers presented results from a study of 105 patients with advanced gastric cancer who were treated with nivolumab as a ≥3 line of therapy to analyze the clinical implications of TMB and insertion-deletion burden in this study group. The TMB was determined via a panel sequencing platform. From this, the insertion-deletion burden rate was determined. Progression-free survival (PFS) and overall survival (OS) were evaluated and compared among the subgroup populations.
The patient population was 61.9% male and ranged from 32 to 78 years of age, with a median age of 58 years. Patients with a high TMB (≥10/Mb) had a PFS (P = .320) and OS (P = .140) similar to those patients with a low TMB. However, patients with a high insertion-deletion rate (>40%) were found to have a favorable PFS (P = .009) and OS (P = .007) when compared with patients with a lower insertion-deletion rate.
In a subgroup analysis, for those patients with a high TMB, superior PFS (P <.001) and OS (P = .002) values were prominently associated with a high insertion-deletion rate, but this association was not found in the low-TMB group. High TMB and a high insertion-deletion rate and PD-L1 combined positive score ≥1 had an independent association with favorable PFS and OS.
In patients with gastric cancer treated with nivolumab, the insertion-deletion rate was associated with clinical outcomes, including PFS and OS.
Kim H-D, Ryu M, Park Y, et al. Insertion-deletion rate is a qualitative aspect of the tumor mutation burden associated with the clinical outcomes of gastric cancer patients treated with nivolumab. Ann Oncol. 2021;32(suppl_5):S1064-S1065.
- Kim J, Kim B, Kang SY, et al. Tumor mutational burden determined by panel sequencing predicts survival after immunotherapy in patients with advanced gastric cancer. Front Oncol. 2020;10:314.
- Henry NL, Hayes DF. Cancer biomarkers. Mol Oncol. 2012;6:140-146.