Three-Year Follow-Up of Neoadjuvant Programmed Cell Death Protein-1 Inhibitor (Sintilimab) in NSCLC

Introduction: Programmed cell death protein-1 (PD-1) inhibitors have been proved to be feasible and to have efficacy in multiple cancers, including NSCLC. But few studies have evaluated the effectiveness of PD-1 inhibitor as neoadjuvant therapy with a long-term follow-up. Here, in this phase 1b study with a 3-year follow-up, we reported the clinical outcomes of patients who received the PD-1 inhibitor as neoadjuvant therapy. Methods: Two doses of sintilimab (intravenously, 200 mg) were used for patients with stages IA to IIIB NSCLC (registration number: ChiCTR-OIC-17013726). Then, surgery was performed within 29 to 43 days after the first dose. All patients underwent positron emission tomography–computed tomography at enrolment and before surgery to evaluate tumor metabolism after administration of PD-1 inhibitor. We also evaluated the expression of programmed death-ligand 1 (PD-L1) as an exploratory analysis in 32 eligible patients. Safety was the primary end point. Overall survival (OS), disease-free survival (DFS), event-free survival, and major pathologic response were the key secondary end points. Results: With the mean follow-up of 37.8 months, 3-year OS rate was 88.5% and the 3-year DFS rate was 75.0% among patients who underwent R0 resection. In patients with positive PD-L1 expression, 3-year OS and DFS rates were 95.5% and 81.8%, respectively. Eight patients had recurrent tumors, including local recurrence, lung metastasis, brain metastasis, and bone metastasis. Patients with PD-L1 greater than or equal to 1% had more favorable clinical outcomes than the other subgroup (hazard ratio = 0.275, 95% confidence interval: 0.078–0.976). No more new adverse events have occurred in the 3-year follow-up because we first reported them in the former publication. Conclusions: This is the first study to report the long-term survival probability of patients with NSCLC receiving PD-1 inhibitors as the neoadjuvant treatment. The 3-year follow-up results revealed that patients with positive PD-L1 expression and high tumor mutation burden have favorable clinical outcomes.