ctDNA clearance (CL) during neoadjuvant treatment (neoadj Tx) and its association with outcomes in patients (pts) with resectable/borderline resectable stage IIB–IIIB NSCLC from MDT-BRIDGE

MDT-BRIDGE

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In patients with resectable or borderline resectable stage IIB-IIIB NSCLC receiving neoadjuvant durvalumab plus chemotherapy, ctDNA clearance before surgery or chemoradiotherapy was associated with higher pathological complete response rates and better 12-month event-free and progression-free survival.

N

142pazienti

Disegno

Phase 2 non-randomised study (NCT05925530) in treatment-naïve EGFR/ALK wild-type patients with resectable or borderline resectable stage IIB-IIIB NSCLC: all received neoadjuvant durvalumab plus chemotherapy, then surgery and adjuvant durvalumab if resectable at multidisciplinary reassessment, or chemoradiotherapy and consolidation durvalumab if unresectable.

Esito

ctDNA clearance from baseline (pre-treatment) to pre-surgery or pre-chemoradiotherapy and other neoadjuvant timepoints, measured with an ultrasensitive assay (LoD95 ≤1 ppm VAF), and its association with pCR, EFS and PFS.

RisultatoOf 142 patients in the full analysis set, 107 had ctDNA assays developed and 99.1% were ctDNA positive at baseline. Median VAF decreases of 96-97% occurred by C2D1 regardless of baseline resectability. ctDNA clearance at pre-surgery/CRT was 36.7% (resectable at reassessment 40.6% vs unresectable 23.8%). The positive predictive value of ctDNA clearance at C2D1 for pCR was 83.3% (95% CI 43.6-99.1). Pre-surgery clearance was 76.0% in patients with pCR (n=25) vs 20.9% in those without pCR (n=43). Among resected patients, none with pre-surgery clearance had an EFS event, while 12-month EFS without clearance was 88.9% (95% CI 72.8-95.7). Among chemoradiotherapy-treated patients, 12-month PFS was 100.0% (95% CI 100.0-100.0) with pre-CRT clearance vs 77.5% (95% CI 44.8-92.3) without.

Spicer J, Gale D, Reck M, et al. Presented at ESMO Congress 2026, abstract LBA62, 26 October. Not yet published.

Discussione e critica

This translational analysis shows that ctDNA falls steeply during neoadjuvant durvalumab plus chemotherapy, and that clearance tracks resectability and pCR. The ctDNA population was 107 of 142 patients, because the assay needed sequencing of a pre-treatment biopsy. The study is non-randomised, the subgroups are small and the wide confidence interval around the 83.3% positive predictive value shows how imprecise it is. Outcome data reach only 12 months, the abstract gives no negative predictive value or sensitivity, and the claimed improvement over earlier studies is a cross-study comparison, so it is untested whether ctDNA-guided decisions would change outcomes.