Blood-based comprehensive genomic profiling (CGP)

Blood-based comprehensive genomic profiling (CGP) assay may tackle the significant challenges in NSCLC management, 1) insufficient tumor tissue for molecular testing; 2) complexity of genotype related treatment decision, see bTMB and BFAST [102P]

Although recent data suggest that tumor mutational burden (TMB) has shown clinical utility in predicting outcomes for patients treated with anti-PDL1/PD1 therapies, such analyses require quality tumor tissue that in many cases is not available for patients diagnosed in the metastatic setting, which is a gap in diagnosis remains unresolved.

In this study, Fabrizio et al developed and analytically validated a blood-based assay to determine TMB from the circulating tumor DNA (ctDNA) derived from blood (bTMB) with high accuracy and precision from as little as 1% tumor content in 20 ng of cfDNAThe average PPA, NPA and PPV across both bTMB cutoffs was 95%, 100% and 100%, respectively. The average precision was 96%, with a coefficient of variation of 17% across all replicates. Clinical validation of bTMB will be established in a prospective, randomized phase III clinical trial in 1L NSCLC comparing the anti-PD-L1 agent, atezolizumab, against standard of care platinum-based doublet chemotherapy (BFAST click for detail).

BFAST is a multi-center prospective umbrella study in 1L NSCLC using CGP assay for bTMB, currently ongoing (NCT03178552). Inspiringly, three centers of Hong Kong participated this global clinical trial. An abstract was presented by ​T. Moket. al. in ESMO 2017 (B-F1RST and BFAST enable clinical development of novel blood-based biomarker assays for tTMB and somatic mutations in 1L advanced or metastatic NSCLC).

Charmaine Ye
Senior Officer, Medical Affairs
Foundation Medicine