학술논문
Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non–Small Cell Lung Cancer
Document Type
article
Author
Hu-Lieskovan, Siwen; Lisberg, Aaron; Zaretsky, Jesse M; Grogan, Tristan R; Rizvi, Hira; Wells, Daniel K; Carroll, James; Cummings, Amy; Madrigal, John; Jones, Benjamin; Gukasyan, Jacklin; Shintaku, I Peter; Slamon, Dennis; Dubinett, Steven; Goldman, Jonathan W; Elashoff, David; Hellmann, Matthew D; Ribas, Antoni; Garon, Edward B
Source
Clinical Cancer Research. 25(16)
Subject
Language
Abstract
PurposeSeveral biomarkers have been individually associated with response to PD-1 blockade, including PD-L1 and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and CD8 cells in melanoma. We sought to examine the relationship between these distinct variables with response to PD-1 blockade and long-term benefit.Experimental designWe assessed the association between baseline tumor characteristics (TMB, PD-L1, CD4, and CD8) and clinical features and outcome in 38 patients with advanced NSCLC treated with pembrolizumab (median follow-up of 4.5 years, range 3.8-5.5 years).ResultsPD-L1 expression and CD8 infiltration correlated with each other and each significantly associated with objective response rate (ORR) and progression-free survival (PFS). TMB was independent of PD-L1 and CD8 expression, and trended towards association with ORR and PFS. There was no association between CD4 infiltration and outcomes. Only PD-L1 expression was correlated with overall survival (OS). Among 5 patients with long-term survival >3 years with no additional systemic therapy, PD-L1 expression was the only discriminating feature. The increased predictive value for PFS and OS of composite biomarker inclusive of PD-L1, CD8, CD4, and TMB was limited.ConclusionsIn patients with NSCLC treated with PD-1 blockade with long-term follow up, TMB, PD-L1, and CD8 were each associated with benefit from PD-1 blockade. Pretreatment PD-L1 expression was correlated with T lymphocyte infiltration and OS, whereas models incorporating TMB and infiltrating CD4 and CD8 lymphocytes did not substantially add to the predictive value of PD-L1 alone for OS.