Dynamic circulating tumor DNA indicates pathological benefits of additional neoadjuvant chemoimmunotherapy courses for locally advanced non-small-cell lung cancer patients

TL;DR

This study shows that tracking circulating tumor DNA can help determine if more chemotherapy and immunotherapy cycles benefit lung cancer patients.

Contribution

The study introduces ctDNA-based MRD as a novel biomarker to guide optimal neoadjuvant chemoimmunotherapy cycles in locally advanced NSCLC.

Findings

Patients who eliminated ctDNA-MRD after two cycles had higher pCR rates with additional therapy.

ctDNA-MRD correlated strongly with radiological assessment in the four-cycle NCI group.

Subgroups with persistent ctDNA-MRD had the lowest pCR rates.

Abstract

Few studies have focused on the optimal cycles of neoadjuvant chemoimmunotherapy (NCI). This study introduced minimal residual disease (MRD) based on circulating tumor DNA (ctDNA), and investigated the association between ctDNA-MRD and NCI cycles and pathological response.

This study was based on a phase III trial (NCT05157776). The patients with IIIA NSCLC without driver genes were given two cycles of NCI (initial two-cycle NCI), after which they were 1:1 randomly assigned to the two-cycle NCI groups (no additional NCI) or four-cycle NCI group (with another two cycles of NCI).

This study involved 13 patients with 28 blood samples. At the start of the study, ctDNA-MRD was detected in 10 out of the 13 patients (77%). The pathologically complete response (pCR) rate was higher in the four-cycle NCI group (3/6, 50%) than in the two-cycle NCI group (1/7, 14.2%). Remarkably, the subgroup that achieved ctDNA-MRD elimination after two cycles and kept elimination after additional two cycles had the highest pCR rate (3/4, 75.0%). Correspondently, the subgroup that did not achieve ctDNA-MRD elimination after two cycles and kept existence after additional two cycles had the lowest pCR rate (0/2, 0%). Generally, in the four-cycle group, a strong correlation between ctDNA-MRD and radiological assessment was observed (5/6, 83.3%).

Patients with locally advanced NSCLC who achieved ctDNA-MRD elimination after two-cycle NCI were more likely to benefit from additional two-cycle NCI, manifesting higher pCR rates. ctDNA-MRD could be a promising tool to determine the optimal cycle of NCI.

Clinicaltrial.gov, NCT05157776.

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