Progression‑free survival for unresectable non‑metastatic locally advanced pancreatic cancer after surgical microwave ablation plus durvalumab and tremelimumab: phase-2 non-randomized prospective clinical trial
The combination of surgical microwave ablation with dual immune‑checkpoint inhibitors durvalumab and tremelimumab improves progression‑free survival in patients with unresectable non‑metastatic locally advanced pancreatic cancer.
Background: Despite significant advancements in cancer immunotherapy, survival outcomes remain poor in patients with pancreatic ductal adenocarcinoma. Methods: In this early phase II clinical trial, we evaluated the combined effects of immunotherapy with dual immune checkpoint inhibitors durvalumab and tremelimumab, local tumor ablation with microwave energy, and gemcitabine on progression‑free survival in twelve patients with non‑metastatic unresectable locally advanced pancreatic adenocarcinoma. Results: Twelve patients were treated; median progression‑free survival was 8.9 months (95% CI 3.2–18.4). Eight patients received the full combination regimen, with a median progression‑free survival of 11.2 months (95% CI 4.0–18.4). Single‑cell transcriptomics and T‑cell receptor profiling revealed a high CD8‑Temra gene signature associated with improved overall survival. Conclusions: CD8‑Temra cells may serve as potential biomarkers and therapeutic targets for immunotherapy efficacy in pancreatic ductal adenocarcinoma, pending validation in larger cohorts.
Our findings suggest that combining local tumor ablation with immunotherapy may enhance the body’s anti‑tumor immune response, but larger studies are needed to confirm these results.
Evidence level: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.