In resectable non-small cell lung cancer, treatment response may become visible in the bloodstream before surgery. New biomarker analyses from CheckMate 77T link pre-surgical circulating tumour DNA clearance and pathological response with outcomes after perioperative nivolumab, while highlighting both the potential—and current limitations—of molecular monitoring.
Perioperative nivolumab has already demonstrated improved event-free survival in resectable non-small cell lung cancer (NSCLC). A new analysis of the phase III CheckMate 77T trial asks a more targeted question: which biomarkers may help identify patients deriving benefit?
A new research published by Associate Professor Tina Cascone (University of Texas MD Anderson Cancer Center, USA), found that among 190 biomarker-evaluable patients – 41% of the randomized population – circulating tumour DNA (ctDNA) provided one of the clearest signals. Pre-surgical ctDNA clearance occurred in 66% of evaluable patients receiving nivolumab plus chemotherapy, compared with 38% receiving placebo plus chemotherapy. Among patients with clearance, pathological complete response occurred in 50% and 12%, respectively.
Post-surgical molecular residual disease was also informative. Thirteen initially MRD-negative patients became MRD-positive during adjuvant treatment, and all subsequently experienced disease recurrence. Exploratory analyses further suggested nivolumab benefit in tumours carrying alterations in KEAP1, STK11, CDKN2A and/or SMARCA4, although subgroup sizes were limited.
Machine-learning modelling ranked pre-surgical ctDNA clearance, nodal status, pathological complete response, tumour histology and nivolumab treatment among the strongest predictors of event-free survival.
The findings support combining dynamic molecular measurements with pathological and clinical information rather than relying on a single genomic marker. However, the biomarker analyses were exploratory, included fewer than half of randomized patients and require prospective validation before informing routine treatment decisions.
Reference
Cascone, T. et al. “Biomarkers of nivolumab benefit in resectable non-small cell lung cancer.” Nature (2026). DOI: 10.1038/s41586-026-10925-6.
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