Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2018 Apr 17

PMID 29657128

Citations 604

Authors

Matthew D Hellmann

Tavi Nathanson

Hira Rizvi

Benjamin C Creelan

Francisco Sanchez-Vega

Arun Ahuja

Ai Ni

Jacki B Novik

Levi M B Mangarin

Mohsen Abu-Akeel

Cailian Liu

Jennifer L Sauter

Natasha Rekhtman

Eliza Chang

Margaret K Callahan

Jamie E Chaft

Martin H Voss

Megan Tenet

Xue-Mei Li

Kelly Covello

Andrea Renninger

Patrik Vitazka

William J Geese

Hossein Borghaei

Charles M Rudin

Scott J Antonia

Charles Swanton

Jeff Hammerbacher

Taha Merghoub

Nicholas McGranahan

Alexandra Snyder

Jedd D Wolchok

Affiliations

Soon will be listed here.

Abstract

Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis. The low response rate in TMB low NSCLCs demonstrates that combination immunotherapy does not overcome the negative predictive impact of low TMB. This study demonstrates the association between TMB and benefit to combination immunotherapy in NSCLC. TMB should be incorporated in future trials examining PD-(L)1 with CTLA-4 blockade in NSCLC.

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