Background: Immune checkpoint inhibitors (ICIs) have become the standard treatment for advanced non-small cell lung cancer (NSCLC). ICIs can provide durable responses and prolong survival for some patients. With the increasing routine of next-generation sequencing (NGS) in clinical practice, it is essential to integrate prognostic factors to establish novel nomograms to improve clinical prediction ability in NSCLC with ICIs treatment.

Methods: Clinical information, response data, and genome data of advanced NSCLC treated ICIs were obtained from cBioPortal. The top 20 gene alterations in durable clinical benefit (DCB) were compared with those genes in no durable benefit (NDB). Survival analyses were performed using the Kaplan-Meier plot method and selected clinical variables to develop a novel nomogram.

Results: The mutation of PTPRD was significantly related to progression free survival (PFS) and overall survival (OS) in advanced NSCLC with ICIs treatment (PFS: p = 0.0441, OS: p = 0.0086). The PTPRD mutation was closely related to tumor mutational burden (TMB) and tumor-infiltrating immune cells (TIICs). Two novel nomograms were built to predict the PFS and OS of advanced NSCLC patients with ICIs treatment.

Conclusions: Our study suggested that PTPRD mutations could serve as a predictive biomarker for the sensitivity to ICIs treatment and PFS and OS in advanced NSCLC with ICIs. Our systematic nomograms showed great potential value in clinical application to predict the PFS and OS for advanced NSCLC patients with ICIs.