Tumor Characteristics Associated with Benefit from Pembrolizumab in Advanced Non–Small Cell Lung Cancer

Siwen Hu‐Lieskovan(University of California, Los Angeles), Aaron Lisberg(University of California, Los Angeles), Jesse M. Zaretsky(University of California, Los Angeles), Tristan Grogan(University of California, Los Angeles), Hira Rizvi(Kettering University), Daniel K. Wells(Parker Institute for Cancer Immunotherapy), James Carroll(University of California, Los Angeles), Amy L. Cummings(University of California, Los Angeles), John Madrigal(University of California, Los Angeles), Benjamin Jones(University of California, Los Angeles), Jaklin Gukasyan(University of California, Los Angeles), I. Peter Shintaku(University of California, Los Angeles), Dennis J. Slamon(University of California, Los Angeles), Steven M. Dubinett(University of California, Los Angeles), Jonathan W. Goldman(University of California, Los Angeles), David Elashoff(University of California, Los Angeles), Matthew D. Hellmann(Cornell University), Antoni Ribas(University of California, Los Angeles), Edward B. Garon(University of California, Los Angeles)
Clinical Cancer Research
May 21, 2019
10.1158/1078-0432.ccr-18-4275
Cited by 72Open Access
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Abstract

PURPOSE: Several 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 DESIGN: We 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). RESULTS: PD-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. CONCLUSIONS: In 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.

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