Oncology · Pulmonology · 2 h ago
NeoCOAST-2 links ctDNA clearance with outcomes in resectable lung cancer
A prespecified secondary analysis of the phase 2 randomized platform trial NeoCOAST-2 assessed event-free survival (EFS) and circulating tumor DNA (ctDNA) clearance in patients with stage IIA–IIIB resectable non-small cell lung cancer. ctDNA clearance was associated with longer EFS; the datopotamab deruxtecan combination had numerically highest clearance and 24-month EFS rates among the reported arms.
- ctDNA clearance was associated with longer event-free survival.
- Dato-DXd arm had numerically highest ctDNA clearance and 24-month EFS.
- Combined ctDNA clearance and pCR identified a group with favourable EFS.
NeoCOAST-2 (NCT05061550) was a phase 2 randomized platform trial of perioperative treatment for resectable stage IIA–IIIB non-small cell lung cancer. This report presents prespecified secondary analyses of EFS and ctDNA clearance, plus exploratory analyses of their association. Three combinations of chemotherapy and durvalumab were assessed: with oleclumab (Arm 1, n=76), monalizumab (Arm 2, n=72), or datopotamab deruxtecan (Dato-DXd; Arm 4, n=54).
Reported 24-month EFS rates were 70.5%, 75.7%, and 77.9% in Arms 1, 2, and 4, respectively. ctDNA clearance at neoadjuvant Cycle 3 Day 1 was 50.9%, 54.5%, and 72.5%. Across the pooled arms, ctDNA clearance was associated with longer EFS than no clearance (hazard ratio 0.22; 95% CI 0.11–0.45). Patients with both ctDNA clearance and pathological complete response had better EFS than those with neither (HR 0.10; 95% CI 0.02–0.42).
These findings support further evaluation of ctDNA dynamics for risk stratification, but the reported associations do not establish that ctDNA-guided treatment improves outcomes. The Dato-DXd arm’s results were numerically highest, and the authors state that they warrant further evaluation; these phase 2 findings alone do not establish comparative superiority or a change in practice.
In practice
For patients with resectable stage IIA–IIIB NSCLC treated in NeoCOAST-2, ctDNA clearance after neoadjuvant treatment was associated with longer EFS, and combined ctDNA clearance and pathological complete response identified a group with more favourable EFS. These results may inform further study of postoperative risk stratification, but do not show that ctDNA-guided decisions improve outcomes. The evidence is from secondary and exploratory analyses of a phase 2 trial; the numerically higher Dato-DXd results do not establish comparative superiority or justify changing treatment.
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Nature: ctDNA clearance and outcomes for resectable lung cancer from NeoCOAST-2 ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.