Validation of the Combined Biomarker for Prediction of Response to Checkpoint Inhibitor in Patients with Advanced Cancer.

Although immune checkpoint inhibitors can induce durable responses in patients with multiple types of advanced cancer, only a limited number of patients have a known reliable biomarker. This study aimed to validate the IMmunotherapy Against GastrIc Cancer (IMAGiC) model, which was developed based on a previous study of four-gene and PD-L1 level, to predict immunotherapy response. We developed a clinical assay for formalin-fixed paraffin-embedded samples using quantitative real-time polymerase chain reaction to measure the expression level of the previously published four-gene set. The predictive performance was validated in a cohort of 89 patients with several advanced tumor types. The IMAGiC score was derived from tumor samples of 89 patients consisting of eight cancer types, and 73 out of 89 patients available for clinical response were analyzed with clinicopathological factors. The IMAGiC group (responder vs. non-responder) was determined with a specific value of the IMAGiC score as a cutoff, which was set by log-rank statistics for progression-free survival (PFS) divided the patients into 56 (76.7%) non-responders and 17 (23.3%) responders. Clinical responders (complete response/partial response) were higher in the IMAGiC responder group than in the non-responder group (70.6 vs. 21.4%). The median PFS of the IMAGiC responder group and non-responder was 20.8 months (95% CI 9.1-not reached) and 6.7 months (95% CI 4.9-11.1, = 0.007), respectively. Among the 17 IMAGiC responders, 11 patients had tumor mutation burden-low and microsatellite-stable tumors. This study validated a predictive model based on a four-gene expression signature. Along with conventional biomarkers, our model could be useful for predicting response to immunotherapy in patients with advanced cancer.