Efficacy and safety of intra-arterial liver–directed therapies in unresectable neuroendocrine carcinoma liver metastases.

e16308 Background: Neuroendocrine carcinoma (NEC) is an aggressive malignancy characterized by rapid progression and high metastatic potential, leading to a dismal median overall survival (OS) of only 11–12 months in patients with metastatic disease. Platinum-based chemotherapy with etoposide plus cisplatin or carboplatin remains the standard first-line treatment; however, its clinical benefit is modest, with an objective response rate (ORR) of approximately 31% and a median progression-free survival (PFS) of merely 4 months, and no established second-line therapy is currently available, underscoring a substantial unmet clinical need. Although intra-arterial liver-directed therapies (IALT) are routinely used to treat liver metastases from well-differentiated neuroendocrine tumors, their efficacy and safety in poorly differentiated and highly proliferative neuroendocrine carcinoma liver metastases (NECLM) remain largely undefined. This study aimed to evaluate the clinical outcomes and safety of IALT in patients with NECLM. Methods: 30 patients with pathologically confirmed NECLM who underwent IALT at Peking University Cancer Hospital from February 2012 to November 2024 were retrospectively analyzed. Treatment modalities included transarterial chemoembolization (TACE) alone (n = 5), transarterial embolization (TAE) alone (n = 2), hepatic arterial infusion chemotherapy (HAIC) alone (n = 1), TACE combined with HAIC (n = 20) and TAE combined with HAIC (n = 2). The primary endpoint was PFS while secondary endpoints included hepatic PFS (hPFS), OS, ORR, disease control rate (DCR) and safety. Results: The study cohort exhibited a substantial disease burden, with 83.3% of patients presenting with synchronous liver metastases and 76.7% with extrahepatic disease; moreover, 86.7% had received prior systemic therapy. The intervention achieved an ORR of 36.7% and a DCR of 70.0%. Median OS was 8.35 months, while median hPFS and PFS were 5.1 months and 4.5 months, respectively. No treatment-related deaths occurred. Grade ≥3 adverse events were generally manageable and most commonly consisted of transaminase elevation (18.9%), abdominal pain (17.0%) and hyperbilirubinemia (7.5%). Conclusions: IALT demonstrated acceptable safety and modest efficacy in the high-risk NECLM patients with aggressive disease and limited therapeutic options. These results indicate that IALT may serve as a feasible locoregional treatment strategy for NECLM, warranting further investigation to refine patient selection and optimize treatment approaches.