Neoadjuvant PD-1 Blockade Tislelizumab (BGB-A317) in Combination With Etoposide and Platinum-Based Chemotherapy for Limited-Disease Small Cell Lung Cancer.

Neoadjuvant immunochemotherapy has transformed treatment paradigms in non-small cell lung cancer, yet its applicability in limited-disease small cell lung cancer (LD-SCLC) remains unknown. Here, we report findings from LungMate-006, the first prospective Phase II trial evaluating PD-1 blockade with tislelizumab combined with platinum-etoposide in LD-SCLC. Among 15 enrolled patients, the regimen achieved an objective response rate of 66.7% and enabled curative-intent surgery in 60% of patients, all with R0 resection. Major pathological response and pathological complete response occurred in 44.4% and 33.3% of surgical cases, respectively. Median event-free and overall survival reached 21.7 and 32.7 months. Metabolic response by PET-CT more accurately predicted pathological remission than radiographic shrinkage alone. Bulk RNA sequencing revealed a treatment-induced transition from a metabolically active baseline state toward an extracellular matrix-remodeled, CAF- and macrophage-enriched microenvironment, alongside upregulation of genes associated with tumor stemness and immune evasion. These transcriptomic changes suggest stromal-myeloid-mediated adaptive resistance in non-MPR tumors and highlight potential avenues for refining perioperative immunochemotherapy strategies in SCLC.