Cancer Cell
Volume 33, Issue 5, 14 May 2018, Pages 843-852.e4
Journal home page for Cancer Cell

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

https://doi.org/10.1016/j.ccell.2018.03.018Get rights and content
Under a Creative Commons license
open access

Highlights

  • High TMB correlates with efficacy of PD-1 plus CTLA-4 blockade in NSCLC

  • TMB and PD-L1 are independent variables

  • In multivariate analysis, TMB associated most strongly with efficacy

Summary

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.

Keywords

immunotherapy
mutation burden
TMB
lung cancer
PD-1
CTLA-4

Cited by (0)

17

Lead Contact