Neoadjuvant serplulimab combined with chemotherapy in locally advanced driver gene-negative squamous NSCLC: a multicenter observational study

Background Previous evidence demonstrated that neoadjuvant chemo-immunotherapy provides significant prognostic benefits for non-small cell lung cancer (NSCLC). While the efficacy of serplulimab, an anti-PD-1 monoclonal antibody, has been well established in advanced driver gene-negative NSCLC in the ASTRUM-004 trial, its efficacy in the neoadjuvant setting remains unclear. This real-world study aims to evaluate the efficacy and safety of neoadjuvant serplulimab plus chemotherapy in patients with locally advanced squamous NSCLC, with a particular focus on pathological response outcomes. Methods This was a multicenter, retrospective–prospective, real-world observational study. Electronic medical records were retrospectively reviewed to identify eligible patients with locally advanced squamous NSCLC who received at least 1 cycle of neoadjuvant serplulimab (300 mg, Q3W) combined with platinum–taxane chemotherapy. Prospective follow-up was conducted to complete courses and outcomes. The primary endpoint was major pathologic response (MPR), and the secondary endpoints included pathological complete response (pCR), objective response rate (ORR), event-free survival (EFS), overall survival (OS), and safety. Results Thirty patients were included (median age 64 years; 96.7% male; 86.7% stage III). Most patients received two cycles of neoadjuvant therapy (46.67%), and 80% achieved a radiologic ORR (95% CI, 61.4–92.3%). Surgery was performed on 28 patients (93.33%), with MPR and pCR achieved in 57.1% (95% CI, 39.1–73.5%) and 28.6% (95% CI, 15.3–47.1%), respectively, and an R0 resection rate of 92.9%. Compared with the historical chemotherapy group, the observed MPR was significantly higher (57.1% vs 8.9% and 11.0%; P < 0.001). The median EFS reached 29.97 months, and the 12-month EFS rate was 91.8% (95% CI, 81.4–100%). The OS data were immature. Grade 3 adverse events occurred in 6.7% of patients, and no grade 4–5 events or perioperative immune-related complications were reported. Exploratory analyses revealed that a lower post-treatment neutrophil-to-lymphocyte ratio (NLR< 3) was positively correlated with MPR, whereas advanced T stage (T3–T4) was negatively associated. Conclusion Neoadjuvant serplulimab-chemotherapy demonstrated promising efficacy and manageable toxicity in real-world locally advanced NSCLC. Survival outcomes require longer follow-up to assess clinical benefit.