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

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 mutatio...

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Detalles Bibliográficos
Autores principales: Hellmann, Matthew D., Nathanson, Tavi, Rizvi, Hira, Creelan, Benjamin C., Sanchez-Vega, Francisco, Ahuja, Arun, Ni, Ai, Novik, Jacki B., Mangarin, Levi M.B., Abu-Akeel, Mohsen, Liu, Cailian, Sauter, Jennifer L., Rekhtman, Natasha, Chang, Eliza, Callahan, Margaret K., Chaft, Jamie E., Voss, Martin H., Tenet, Megan, Li, Xue-Mei, Covello, Kelly, Renninger, Andrea, Vitazka, Patrik, Geese, William J., Borghaei, Hossein, Rudin, Charles M., Antonia, Scott J., Swanton, Charles, Hammerbacher, Jeff, Merghoub, Taha, McGranahan, Nicholas, Snyder, Alexandra, Wolchok, Jedd D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953836/
https://www.ncbi.nlm.nih.gov/pubmed/29657128
http://dx.doi.org/10.1016/j.ccell.2018.03.018
Descripción
Sumario: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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