Five-year follow-up of neoadjuvant PD-1 inhibitor (sintilimab) in non-small cell lung cancer.

Background: Neoadjuvant anti-programmed cell death protein-1 (PD-1) therapy exhibits potential in treating resectable non-small cell lung cancer (NSCLC). Previously, we have reported the 3-year clinical outcomes of this trial, implying the effectiveness and feasibility of neoadjuvant sintilimab monotherapy. However, the long-term prognosis of patients receiving neoadjuvant mono-immunotherapy has yet to be elucidated.

Methods: For patients with stage IA-IIIB NSCLC, two doses of sintilimab (200 mg) were administered intravenously in the neoadjuvant setting. The 5-year event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were assessed in these updated results. The predictive role of specific biomarkers in neoadjuvant immunotherapy was also explored.

Results: With a median follow-up of 61.0 months, 5-year DFS and OS rates of patients who underwent R0 resection were 65.7% and 80.4%, respectively. The 5-year DFS and OS rates of patients with positive programmed death-ligand 1 (PD-L1) expression were 71.9% and 90.9%, respectively. The presence of PD-L1 positivity (tumor proportion score ≥1%) showed a tendency toward the promising prognosis (OS, HR, 0.143; 95% CI: 0.027 to 0.743), especially for those who did not achieve pathological complete response (pCR). In addition, tumor mutation burden was positively correlated with a favorable prognosis. A total of 10 recurrences and 5 subsequent deaths were identified within the 5-year follow-up, with lung metastasis being the predominant.

Conclusions: These updated analyses were the first to unveil the 5-year survival benefits of neoadjuvant sintilimab monotherapy, implying the potential value of PD-1 inhibitors in neoadjuvant therapy.