Hellmann, MD;
Nathanson, T;
Rizvi, H;
Creelan, BC;
Sanchez-Vega, F;
Ahuja, A;
Ni, A;
... Wolchok, JD; + view all
(2018)
Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.
Cancer Cell
, 33
(5)
843-852.e4.
10.1016/j.ccell.2018.03.018.
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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.
| Type: | Article |
|---|---|
| Title: | Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ccell.2018.03.018 |
| Publisher version: | https://doi.org/10.1016/j.ccell.2018.03.018 |
| Language: | English |
| Additional information: | © 2018 Francis Crick Institute. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, Anti-PD-1 Checkpoint Blockade, Generation Sequencing Data, Tumor Mutational Burden, PD-1 Blockade, Solid Tumors, Melanoma, Landscape, Nivolumab, Resistance, Ipilimumab |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050826 |
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