PD04.04. Prognostic Significance of B7-H3 Expression in High-Risk Locally Advanced ESCC After Trimodality Therapy and Adjuvant Pembrolizumab: Post-Hoc Analysis
Abstract
Esophageal Cancer: Molecular Biology/Pathology B7-H3 (CD276) is an immunoregulatory molecule and emerging therapeutic target. The prognostic value of B7-H3 expression in locally advanced esophageal squamous cell carcinoma (ESCC) treated with multimodality therapy plus adjuvant pembrolizumab was unclear. We performed a post-hoc analysis of a single-arm phase II ESCC patient cohort (NCT03322267) treated with protocol-specified adjuvant cisplatin-based chemoradiotherapy (CRT) followed by pembrolizumab for post-neoadjuvant CRT esophagectomy, pathology revealing risk factors for recurrence including involved or close margins (≤1 mm), extranodal extension of involved lymph nodes, and ypN2-3 stage. Patients in the study cohort with adequate surgical tissue for B7-H3 immunohistochemistry (IHC) were included. B7-H3 (clone EPR20115, Abcam) was scored by H-score. H-score values of B7-H3 IHC analyses calculated by multiplying the percentage of cells positive by 1, 2 or 3 based on expression intensity. PD-L1 combined positive score (CPS) was assessed with Dako 22C3. Relapse-free survival (RFS) and overall survival (OS) were analyzed. Cox proportional hazards models adjusted for age, performance status, post-neoadjuvant therapy pathology stage, margin status, lymphovascular invasion, perineural invasion, tumor regression grade, and PD-L1 expression. Twenty-four patients were evaluable (B7-H3 H-score ≥150: n=7; <150: n=17). PD-L1 CPS was similar between the B7-H3 H-score ≥150 vs <150 groups (median 5.0 vs 4.0; p=0.637). B7-H3 H-score ≥150 was associated with shorter RFS (median 4.6 vs 18.0 months; p =0.002) and OS (median 10.2 vs 19.8 months; p =0.041). In multivariable Cox model, B7-H3 H-score ≥150 independently predicted inferior RFS (p =0.039) but not OS (p =0.108). PD-L1 CPS ≥10 was not significant for RFS (p =0.253) or OS (p =0.428). High tumor B7-H3 (H-score ≥150) identified a higher-risk subgroup with shorter RFS after multimodality therapy plus adjuvant pembrolizumab, independent of PD-L1 CPS and adverse pathologic features, supporting B7-H3 expression for risk stratification and warranting external validation.