Transarterial infusion chemotherapy combined with lenvatinib and tislelizumab versus intravenous chemotherapy for unresectable pancreatic ductal adenocarcinoma: a retrospective propensity score matching analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies with dismal prognosis for unresectable cases. Systemic chemotherapy shows limited efficacy, while transarterial infusion chemotherapy (HAIC) enables targeted drug delivery, and the combination of anti-angiogenic agents and immune checkpoint inhibitors has demonstrated synergistic effects in solid tumors. METHODS: In this retrospective, single-center propensity score-matched study, 183 unresectable PDAC patients treated between January 2021 and December 2024 were analyzed Propensity score matching (PSM) was performed at a 1:1 ratio, resulting in 45 patients in the HAIC + lenvatinib + tislelizumab group and 45 patients in the intravenous chemotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: After PSM, baseline characteristics were well-balanced.1). The HAIC + lenvatinib + tislelizumab group achieved significantly higher ORR (37.8% vs. 17.8%, P = 0.023) and DCR (88.9% vs. 64.4%, P = 0.004) than the chemotherapy group. Median OS was 13.1 months (95% CI: 11.4-14.7) in the experimental group versus 8.8 months (95% CI: 7.1-10.9) in the control group (P<0.001). Median PFS was 6.0 months (95% CI: 5.0-6.9) versus 3.7 months (95% CI: 1.9-4.0), respectively (P<0.001). The most common grade ≥3 adverse events were hypertension (15.6% vs. 2.2%, P = 0.012) in the HAIC + lenvatinib + tislelizumab group and neutropenia (24.4% vs. 6.7%, P = 0.008) in the chemotherapy group. CONCLUSIONS: HAIC combined with lenvatinib and tislelizumab significantly was associated with significantly prolonged survival and improved tumor response in unresectable PDAC with manageable toxicity, providing a promising therapeutic strategy for this devastating disease.