Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Immune checkpoint inhibitors have transformed anticancer pharmacotherapy, with nivolumab demonstrating significant immunomodulatory potential when combined with cytotoxic agents. However, real-world pharmacological evidence regarding the safety, tolerability and biomarker-guided response of neoadjuvant nivolumab combined with platinum-based chemotherapy in resectable non-small cell lung cancer (NSCLC) remains limited. This study aimed to evaluate the pharmacological efficacy, safety profile and predictive biomarker associations of this combination regimen in clinical practice. Methods: A multicenter retrospective pharmacological outcome study was conducted in 58 patients with stage IB–IIIB resectable NSCLC who received four cycles of neoadjuvant nivolumab in combination with platinum-based chemotherapy. The primary pharmacodynamic endpoint was major pathological response (MPR), serving as a surrogate marker of drug efficacy. Secondary endpoints included pathological complete response (pCR), treatment completion rate, post-treatment surgical resectability and incidence of adverse drug reactions graded according to CTCAE v5.0. Programmed death-ligand 1 (PD-L1) expression and KRAS mutation status were evaluated as predictive biomarkers of drug response. Results: The median patient age was 60 years, with male predominance (70.7%). Adenocarcinoma was the most prevalent histological subtype (60.3%). High PD-L1 expression (?50%) was observed in 31.5% of patients, while KRAS mutations were detected in 44.8%. Curative surgical resection was achieved in 77.6% of patients following neoadjuvant pharmacotherapy. MPR and pCR rates were 43.1% and 29.3%, respectively, with significantly higher response rates observed in patients exhibiting elevated PD-L1 expression. Grade ?3 adverse drug reactions occurred in 17.2% of patients, with no treatment-related mortality, indicating an acceptable safety and tolerability profile. Conclusion: Neoadjuvant nivolumab combined with platinum-based chemotherapy demonstrates favorable pharmacological efficacy, manageable toxicity and biomarker-driven therapeutic response in resectable NSCLC under real-world clinical conditions. These findings support the role of personalized immunopharmacotherapy and reinforce the clinical relevance of biomarker-guided drug selection in modern pharmaceutical oncology.