Impact of SPARC expression on treatment response of pembrolizumab and brain metastasis in patients with metastatic non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) often exhibits elevated Secreted Protein Acidic and Cysteine-Rich (SPARC) expression. In this study, we investigated the impact of SPARC expression on clinicopathologic features, pembrolizumab response, and prognosis in metastatic NSCLC patients.

Methods: Thirty-six patients diagnosed with metastatic NSCLC without actionable driver mutation and who received pembrolizumab with or without chemotherapy were included in this study. PD-L1 and SPARC expression were evaluated, with PD-L1 expression categorized based on tumor proportion score and SPARC staining intensity graded as 1+, 2+, and 3 +. Patients' characteristics were compared across groups, and possible predictive markers were determined by binary logistic regression analysis.

Results: No significant associations were found between SPARC expression and smoking status, histopathological tumor type, T and N status, and liver and bone metastasis. Higher SPARC expression was significantly linked to lower brain metastasis rates but higher CNS progression rates (p = 0.022 and p = 0.011, respectively. The objective response rate (ORR) showed a trend of being higher in the SPARC 1 + group (85.7% vs. 43.8% and 50.0% in 2 + and 3 + groups, respectively, p = 0.052. Univariate analysis did not find SPARC expression to be a significant prognostic factor for progression-free survival (PFS) (p = 0.7) and overall survival (OS) (p = 0.07).SPARC 1 + expression negatively affected the pembrolizumab response(p = 0.04,OR:0.11, 95%CI 0.01-0.92).

Conclusions: Our study sheds light on a novel aspect of SPARC expression as a potential predictor of pembrolizumab response and a marker for CNS progression in metastatic NSCLC patients treated in the first-line setting.