Neoadjuvant chemo‑immunotherapy has improved outcomes in non–small cell lung cancer (NSCLC) by enhancing antigen presentation and reinvigorating systemic immunity. Squamous NSCLC has relatively fewer actionable driver mutations but greater neoantigenicity and immune infiltration, supporting the biological rationale for perioperative immunotherapy. Serplulimab, an anti‑PD‑1 monoclonal antibody, demonstrated benefit in advanced driver gene–negative squamous NSCLC in prior trials, but its efficacy in the neoadjuvant setting was previously unestablished. This multicenter observational study assessed the efficacy and safety of neoadjuvant serplulimab combined with platinum–taxane chemotherapy in real‑world patients with locally advanced, driver gene–negative sq-NSCLC.
This was a multicenter, retrospective–prospective, real‑world observational study conducted at two centers in China. Electronic medical records from June 1, 2023, to May 31, 2024, identified eligible patients; prospective follow-up continued from June 1, 2024, to May 31, 2025 to complete treatment, surgical outcomes, and survival data. Key eligibility criteria included:
Exclusions included prior systemic therapy, palliative intent, unresectable or metastatic disease, recent active malignancy, or critical missing data. The study protocol received institutional ethics approval and patient data were anonymized.
Thirty patients constituted the full analysis set (FAS). Most patients received two cycles of neoadjuvant therapy (46.7%). The taxane component was most commonly nab‑paclitaxel (66.7%) and the platinum agent was most commonly nedaplatin (86.7%). Surgical resection was performed in 28 patients (93.3%); one patient had not yet undergone surgery and one had missing surgical information. Median interval from last neoadjuvant dose to surgery was 6.22 weeks (range 3.57–15.14). Reported reasons for surgical delay included adverse event recovery, imaging reassessment, and patient preference. Median intraoperative blood loss was 100 mL (range 50–300 mL).
All 30 patients had evaluable radiologic assessments. In the FAS, the objective response rate (ORR) was 80.0% (24/30; 95% CI, 61.4–92.3%), comprising 2 complete responses and 22 partial responses; disease control rate was 96.7%.
Among 28 patients who underwent surgery with available pathology (per‑protocol set, PPS), pathological outcomes were:
A predefined one‑sample threshold test comparing observed MPR with historical neoadjuvant chemotherapy benchmarks showed a statistically higher MPR (57.1% observed vs historical 8.9% and 11.0%; P < 0.001). Sensitivity analyses in a subset reflecting typical surgical timelines produced comparable MPR and pCR rates.
Median follow‑up reported in the cohort was limited (median 8.89 months overall; range 0.10–29.97). The median event‑free survival (EFS) reached 29.97 months and the 12‑month EFS rate was 91.8% (95% CI, 81.4–100%). Overall survival (OS) data were immature at the time of reporting. Longer follow‑up is required to ascertain durable survival benefit.
Safety was described as manageable in this cohort. Grade 3 adverse events occurred in 6.7% of patients. No grade 4–5 treatment‑related events or perioperative immune‑related complications were reported. Specific adverse event types and frequencies beyond the grade summary were reported in the source tables but are not elaborated further in this summary beyond the presented aggregate data.
Exploratory regression analyses evaluated clinical factors correlated with MPR. A lower post‑treatment neutrophil‑to‑lymphocyte ratio (post‑treatment NLR < 3) was positively associated with achieving MPR. Conversely, advanced primary tumor stage (clinical T3–T4) was negatively associated with MPR. No statistically significant differences in baseline demographics or most treatment/surgical parameters were observed between MPR and non‑MPR groups in the reported comparisons.
This real‑world observational study reports promising pathological responses with neoadjuvant serplulimab plus chemotherapy in locally advanced, driver gene–negative sq‑NSCLC: a high MPR rate (57.1%), meaningful pCR rate (28.6%), and a high R0 resection frequency (92.9%), with an acceptable safety profile. Limitations include the single‑arm design, small sample size (planned N = 30), limited and immature survival follow‑up, and absence of a randomized comparator in the reported dataset. The source notes that longer follow‑up and prospective randomized data are required to determine whether pathological improvements translate into sustained survival benefit. Details not reported in the source (for example granular adverse event types and long‑term OS) remain unavailable pending extended follow‑up or further studies.