Gene panel guides immune checkpoint inhibitor therapy in NSCLC patients
medwireNews: Researchers report that a cancer gene panel called NCC-GP150 may be able to accurately estimate blood tumor mutational burden (bTMB) in patients with non-small-cell lung cancer (NSCLC), and identify those most likely to benefit from immune blockade therapy.
The NCC-GP150 panel was designed to cover the whole exon regions of 150 selected cancer-related genes, and its ability to determine TMB was compared with that of five established gene panels: MSK-IMPACT, F1CDx, Guardant360, PlasmaSELECT 64, and FoundationACT. Although MSK-IMPACT, which looks at 468 cancer-related genes, showed the best correlation with whole-exome sequencing (WES)-based TMB (r2=0.97), NCC-GP150 showed the next best performance (r2=0.96).
Writing in JAMA Oncology, Jie Wang (Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China) and co-researchers say that “NCC-GP150 […] could be used for bTMB estimation as a surrogate for WES-based TMB, noting that “NCC-GP150 with a smaller panel size and satisfactory performance may be more accessible for clinic use with superior cost-effectiveness.”
And when the NCC-GP150 panel was assessed using published clinical data from 34 patients with NSCLC who had been treated with PD-1 inhibitor therapy, progression-free survival (PFS) was found to be significantly longer among those with a high TMB (ie, greater than the median) than in those with a low TMB, at 14.5 versus 5.2 months (hazard ratio [HR]=0.36).
The reliability of the NCC-GP150 panel’s bTMB calculations was further examined in a technical validation phase of the study, in which 48 patients with advanced NSCLC provided matched tumor tissue and plasma samples for synchronous WES and NCC-GP150 sequencing, respectively. The two tests showed good correlation (Spearman correlation coefficient 0.62), and a bTMB of 6 or higher was found to be the optimal cut-off value.
The researchers then examined whether the NCC-GP150 panel could identify patients who would benefit from immune checkpoint blockade using an independent group of 50 patients with advanced NSCLC treated with PD-1/PD-L1 inhibitor therapy. They found that the 28 patients with a bTMB of at least 6 had a significantly longer median PFS than those with a lower bTMB, at unreached versus 2.9 months (HR 0.39). They were also more likely to experience tumor shrinkage and an objective response, at a rate of 39.3% versus 9.1%.
“Collectively, bTMB measured by the NCC-GP150 panel was confirmed to be a potential [clinically] actionable biomarker for [immune checkpoint blockade] therapy in patients with NSCLC,” conclude the researchers.
By Catherine Booth
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