The third leading cause of cancer-related mortality is gastric cancer and gastroesophageal junction (GEJ) cancer. Most cases are diagnosed at an advanced stage, giving patients an overall poor survival rate if they do not receive treatment. Even with standard treatment, most patients will experience disease progression. This leaves patients with limited treatment options, making the search for new therapies imperative. One avenue of investigational approach is the study of biomarkers that can indicate which tumors may respond to a particular treatment. Lei and colleagues conducted a post-hoc analysis of the gastric/GEJ cohort from the CheckMate-032 clinical trial to evaluate biomarkers that correlated with clinical response to treatment with nivolumab plus ipilimumab.
In the CheckMate-032 study, participants had ≥1 prior chemotherapy regimens and no previous T-cell co-stimulation immune checkpoint inhibitor or antitumor vaccine therapy. Patients were treated with either nivolumab monotherapy or nivolumab in combination with ipilimumab, followed by maintenance nivolumab monotherapy. PD-L1 expression was determined and reported as the percentage of positive tumor cells (%TC). PD-L1 according to combined positive score (CPS) was also determined. In addition, gene expression profiling of 9 inflammatory gene expression signatures or individual transcripts were evaluated during this analysis, including a 4-gene inflammatory signature consisting of CD274 (PD-L1), CD8A, LAG3, and STAT1. There were 40 patients evaluated in this analysis. The evaluation explored the association of PD-L1 expression on tumor and immune cells and inflammatory gene expression signatures with efficacy of nivolumab plus ipilimumab in patients with gastric cancer or GEJ cancer. Efficacy was assessed by evaluating objective responses, objective response rate (ORR), and overall survival.
In the pooled analysis of all treatment regimens, the ORR was 19% for patients with PD-L1–positive tumors with a CPS cutoff of ≥5 and 26% for patients with CPS cutoff ≥10. The ORR was 8% for patients with an equivalent %TC cutoff ≥5 and 9% for patients with an equivalent %TC cutoff ≥10. A longer survival was found in patients with PD-L1–positive versus PD-L1–negative status. In addition, 7 inflammatory gene signature/transcripts, including the 4-gene inflammatory signature, demonstrated associations with a response to nivolumab and ipilimumab.
The post-hoc analysis found a greater association with nivolumab plus ipilimumab therapy efficacy for PD-L1 expression by CPS compared with %TC PD-L1 expression in patients with advanced gastric or GEJ cancer, which may help identify patients who will respond to treatment.
Lei M, Siemers NO, Pandya D, et al. Analyses of PD-L1 and inflammatory gene expression association with efficacy of nivolumab ± ipilimumab in gastric cancer/gastroesophageal junction cancer. Clin Cancer Res. 2021;27:3926-3935.