medwireNews: High nonsynonymous tumor mutation burden (TMB) could identify a favorable prognosis in patients who undergo resection of early-stage non-small-cell lung cancer (NSCLC), and predict who benefits least from adjuvant chemotherapy, research suggests.
In the LACE-Bio II study of 908 resected tumor specimens from three adjuvant clinical trials, patients with a high TMB – defined as more than eight nonsynonymous mutations per megabase (Mb) – had favorable overall survival, disease-free survival (DFS), and lung cancer-specific survival (LCSS), while those with a low nonsynonymous TMB of 4 mutations or less per Mb had poor outcomes.
For instance, the hazard ratio for recurrence or death was 0.88 and 1.20 for patients with high and low TMB, respectively, where both comparisons were with individuals with a moderate TMB (>4 and ≤8 mutations/Mb). The corresponding hazard ratios for lung cancer-specific death were 0.82 and 1.20.
When tumors were categorized by histology, nonsynonymous TMB remained significantly prognostic for LCSS in patients with lung adenocarcinoma and squamous cell carcinoma, and additionally for DFS in squamous cell carcinoma patients.
Interestingly, a further exploratory analysis suggested that patients with low TMB were likely to derive the greatest LCSS benefit from adjuvant chemotherapy, an advantage that decreased with increasing TMB.
“However, this effect may be driven by the small size of samples with high nonsynonymous TMB […] and the linear test for trend was not significant when samples were regrouped by tertiles of TMB,” Ramaswamy Govindan (Washington University School of Medicine, St Louis, Missouri, USA) and colleagues acknowledge in the Journal of Clinical Oncology.
Nonetheless, the team concludes: “Overall, findings from the current study suggest that high nonsynonymous TMB represents a strong and favorable prognostic factor for outcomes in patients with resected NSCLC and could potentially be used to identify patients less likely to benefit from adjuvant chemotherapy.
“Studies are warranted to confirm these observations and explore the mechanisms underlying this association.”
By Anita Chakraverty
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