Shedding light on the molecular determinants of response to anti-PD-1 therapy

Ross A Soo
Translational Lung Cancer Research 2015, 4 (6): 816-9
Immune checkpoint inhibition targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a very promising therapeutic avenue in the treatment of patients with advanced stage non-small cell lung cancer but only a subset of patients derives clinical benefit from PD-1/PD-L1 inhibitors. Studies to date have reported patients with PDL-1 expressing tumors have a better outcome than those with PDL-1 negative tumors but assays used to identify PD-L1 positive patients has been challenging. Through whole exome sequencing of tumors, investigators have recently described mutational burden in non-small cell lung cancer (NSCLC) was associated with response to pembrolizumab. In two independent patient cohorts, it was reported a high somatic nonsynonymous mutation burden was associated with greater durable clinical benefit, higher objective response rates (ORRs) and a longer progression free survival. In addition clinical efficacy was associated with a molecular smoking signature, certain DNA repair mutations and the burden of neoantigens.

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