Validation of the 10-gene expression profile for prediction of response to checkpoint inhibitor in patients with advanced NSCLS

Abstract

Purpose: individualization of the use of immune checkpoint inhibitors in patients with inoperable NSCLC potentially sensitive to immunotherapy based on the level of the combined expression index as a predictive marker of effectiveness.Methods: in 146 patients with inoperable NSCLC, the level of the combined expression index in a tumor tissue sample was determined using PCR, which included studies of ten genes (CCL5, CXCL9, CXCR6, HLA-DQA1, TIGIT, EOMES, CTLA4, PD-L2, GZMB, PRF1). The patients were divided into cohorts depending on the level of the combined expression index and randomized into chemotherapy or immunotherapy groups. The null hypothesis of the study was that the group with a low combined expression index would have a 6-month progression-free survival of 35%, and with a high combined expression index – 75%, with α-error probability of 0.05, a power of 90%. Results: the use immune checkpoint inhibitors in the first line of the therapy for patients with a high level of the combined expression index leads to a significant increase in the rate of objective responses from 18% to 43%, the median overall survival from 10 to 21 months, and the median time to progression from 7.3 to 14.8 months. The 6-month progression-free survival rate in the group with a high combined expression index was 79%, versus 35% in the group with a low combined expression index. Conclusion: analysis of the gene expression signature can become one of the reliable predictive markers that predict the real effectiveness of therapy with immune checkpoint inhibitors, which will improve the results of treatment of patients with unresectable or metastatic NSCLC. Key words: NSCLC, immune checkpoint inhibitors, gene expression signature, predictive markers