Targeted Next-Generation Sequencing for Predicting Treatment Response in Lung Cancer
Targeted next-generation sequencing (NGS) accurately estimates tumor mutation burden in patients with non–small cell lung cancer (NSCLC), according to findings published in the Journal of Clinical Oncology. The study, authored by Matthew D. Hellmann, MD, of the Memorial Sloan Kettering Cancer Center, and colleagues, also found targeted NGS may identify patients most likely to benefit from immune checkpoint inhibitors (ICIs).
Researchers examined 240 patients with NSCLC profiled by NGS and treated with anti–PD-1 or anti–PD-L1–based therapies. Tumor mutation burden, fraction of copy number-altered genome, and gene alterations were compared among patients with durable clinical benefit and no durable benefit.
Estimates of tumor mutation burden by targeted NGS seemed to correlate well with whole-exome sequencing (P = .86), and tumor mutation burden was greater in patients with a durable clinical benefit versus no durable benefit (P = .006). In patients at increasing thresholds above, versus below, the 50th percentile of tumor mutation burden, a durable clinical benefit was more common and progression-free survival longer (38.6% vs. 25.1%). Tumor mutation burden did not correlate with anti–PD-1 expressions, yet both variables had similar predictive capacity.
“It seems that [tumor mutation burden] is similarly meaningful as PD-L1 expression, but a composite of both variables may be most helpful in identifying with precision patients most likely to benefit,” the authors noted.