ctDNA clearance and outcomes for resectable lung cancer from NeoCOAST-2
Menée à partir de données portant sur 202 patients atteints d'un cancer du poumon non à petites cellules de stade IIA-IIIB et inclus dans un essai randomisé de phase II (NeoCOAST-2) évaluant un traitement par chimiothérapie standard et durvalumab en combinaison avec l'oléclumab, le monalizumab ou le datopotamab déruxtécan, cette étude évalue la corrélation entre la clairance de l'ADN tumoral circulant, combinée ou non à la réponse pathologique complète, et la survie sans événement en fonction des combinaisons thérapeutiques
Patients with resectable non-small cell lung cancer (NSCLC) remain at high risk of relapse despite perioperative treatment1-3. NeoCOAST-2 (NCT05061550), a phase 2, randomised platform trial, tested novel perioperative treatments in patients with stage IIA–IIIB NSCLC. At primary analysis, combining standard chemotherapy plus durvalumab (anti-PD-L1 antibody) with oleclumab (Arm 1, n = 76), monalizumab (Arm 2, n = 72) or datopotamab deruxtecan (Dato-DXd; Arm 4, n = 54) resulted in pathological complete response (pCR) rates of 20.3%, 25.7%, and 35.2%, respectively4. Here, we present the first report of prespecified secondary endpoints of event-free survival (EFS) and circulating tumour DNA (ctDNA) clearance, and exploratory analyses of associations between ctDNA dynamics and clinical outcomes. The 24-month EFS rates were 70.5%, 75.7% and 77.9% in Arms 1, 2 and 4, respectively. Using a tumour-agnostic assay, ctDNA clearance at neoadjuvant Cycle 3 Day 1 was highest in Arm 4 (50.9%, 54.5%, and 72.5% in each arm, respectively). ctDNA clearance correlated with prolonged EFS versus non-clearance (pooled hazard ratio (HR) 0.22; 95% CI = 0.11–0.45, P = 0.0000443). Patients with both ctDNA clearance and pCR had favourable EFS outcomes versus those with neither (EFS HR 0.10, 95% CI = 0.02–0.42, P = 0.002). These findings suggest combined assessment of ctDNA clearance and pCR may improve risk stratification, and that the numerically highest pCR4 and EFS rates with the Dato-DXd combination warrant further evaluation.
Nature , article en libre accès, 2026