The Study: Not only is Guardant offering a biopsy-free way to decipher targetable mutations, a new blood test NC-GP150 (with a gene panel size of 150) is promising to quantify overall tumor mutational burden (TMB) all via circulating tumor DNA. In this multi-phase validation study, TMB per NC-GP150 performed on blood samples from 48 patients with NSCLC demonstrated “sufficient” Spearman correlation (0.62) with TMB per the much more invasive and expensive whole genome sequencing performed on matched tissue samples. On exploration of cut-offs, a value of ≥6 mutations per megabase maximized sensitivity and specificity when compared to the whole genome sequencing standard. More importantly, in a separate cohort of 50 patients receiving PD-1 axis inhibition for NSCLC, those with “high” serum TMB (aka ≥6, n=28) achieved significantly higher progression-free survival (HR = 0.34) than those with “low” serum TMB (aka <6, n=22).
Bottom Line: Recognizing the not inconsequential risks of tissue attainment in NSCLC, a liquid biopsy with something like NC-GP150 may soon be enough to buy your patient access to effective PD-1 axis inhibition. | Wang, JAMA Oncol 2019