Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer

BACKGROUND: Immune checkpoint inhibitors (ICIs) are an established treatment for non‐small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested NY‐ESO‐1 and LAG‐3 to be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of their expression in NSCLC. METHODS: We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti‐PD‐1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum‐based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY‐ESO‐1, LAG‐3, and PD‐L1 expression, whose ability to predict progression‐free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values. RESULTS: NY‐ESO‐1 or LAG‐3 expression was detected in all tumor samples from patients with high PD‐L1 expression and was significantly associated with favorable outcomes, unlike PD‐L1 expression. Patients with both NY‐ESO‐1‐ and LAG‐3‐expressing tumors had a high DCB rate and those with triple‐positive PD‐L1, LAG‐3, and NY‐ESO expression had a superior median OS and PFS than those with triple‐negative expression. Furthermore, LAG‐3 and NY‐ESO‐1 co‐expression was an independent predictor of both PFS and OS, while LAG‐3 displayed a good NPV. CONCLUSIONS: Patients with NSCLC who co‐express NY‐ESO‐1 or LAG‐3 with PD‐L1 exhibit greater DCBs and improved long‐term survival following anti‐PD‐1 therapy. Moreover, NY‐ESO‐1 and LAG‐3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.