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

Vollständiger Abstract

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ABSTRACT 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.